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Huber FA, Kell PA, Shadlow JO, Rhudy JL. Cerebral peak alpha frequency: Associations with chronic pain onset and pain modulation. NEUROBIOLOGY OF PAIN (CAMBRIDGE, MASS.) 2025; 18:100180. [PMID: 40124744 PMCID: PMC11925531 DOI: 10.1016/j.ynpai.2025.100180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 01/10/2025] [Accepted: 01/31/2025] [Indexed: 03/25/2025]
Abstract
Chronic pain is highly prevalent in the U.S. and leads to myriad negative sequalae and suffering. One way to address chronic pain is to identify who is at risk and intervene prior to symptom onset. Research suggests resting peak alpha frequency (PAF), the speed of alpha oscillations at rest, is slower in healthy individuals with greater pain sensitivity and in chronic pain patients. Thus, slower PAF may denote chronic pain vulnerability. Other research has shown that individuals at higher risk of chronic pain exhibit disrupted pain modulation, i.e., less efficient pain inhibition and increased pain facilitation. Currently, the ability of PAF to predict chronic pain and its relation to pain modulation is under-researched. This investigation aimed to address this gap by characterizing associations between PAF, onset of chronic pain, and pain modulation. Using archival data from three independent studies, this investigation assessed whether slower PAF is associated with prospectively-determined chronic pain onset, decreased pain inhibition (i.e., impaired conditioned pain modulation, impaired erotica-induced pain inhibition), and increased pain facilitation (i.e., increased temporal summation of pain, augmented mutilation-induced pain facilitation). Results show that slower PAF was associated with greater facilitation of spinal (i.e., nociceptive flexion reflex) and supraspinal (i.e., N2 potential) nociception in response to unpleasant pictures (i.e., human injury images). This suggests that slower PAF is associated with threat-enhanced spinal and supraspinal nociception and may be relevant for chronic pain conditions with disrupted threat systems. Slower PAF was not associated with any other pain outcome, including prospectively determined chronic pain onset. However, chronic pain onset could only be assessed in one study with a mixed eyes open/eyes closed recording, limiting the significance of this finding.
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Affiliation(s)
- Felicitas A. Huber
- Department of Psychology, The University of Tulsa, Tulsa, OK, United States
- Washington University Pain Center, Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
| | - Parker A. Kell
- Department of Psychology, The University of Tulsa, Tulsa, OK, United States
| | - Joanna O. Shadlow
- Department of Psychology, Oklahoma State University, Tulsa, OK, United States
| | - Jamie L. Rhudy
- Department of Psychology, The University of Tulsa, Tulsa, OK, United States
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Marshall A, Elshafei M, Preston FG, Burgess J, Goodson N, Fallon N, Frank B, Zhao SS, Alam U. Small Fibre Pathology in Fibromyalgia: A review. Pain Ther 2025; 14:461-478. [PMID: 39806197 PMCID: PMC11914468 DOI: 10.1007/s40122-024-00696-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Accepted: 11/29/2024] [Indexed: 01/16/2025] Open
Abstract
Fibromyalgia syndrome (FMS) presents a complex and challenging disorder in both the diagnosis and treatment, with emerging evidence suggesting a role of small fibre pathology (SFP) in its pathophysiology. The significance of the role of SFP in FMS remains unclear; however, recent evidence suggests degeneration and dysfunction of the peripheral nervous system, particularly small unmyelinated fibres, which may influence pathophysiology and underlying phenotype. Both skin biopsy and corneal confocal microscopy (CCM) have consistently demonstrated that ~ 50% of people with FMS have SFP. CCM, a non-invasive measure of small nerve fibres has detected small fibre loss, correlating with neuropathic pain descriptors. Additionally, quantitative sensory testing has shown abnormalities, primarily in pain pressure/mechanical pain thresholds. This narrative review provides a comprehensive understanding of the pathophysiological dimensions of FMS with a clear focus on small nerve fibres and the peripheral nervous system, offering a roadmap for future research.
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Affiliation(s)
- Anne Marshall
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, Clinical Sciences Centre, University Hospital Aintree, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool, L9 7AL, UK
| | - Mohamed Elshafei
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, Clinical Sciences Centre, University Hospital Aintree, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool, L9 7AL, UK
| | - Frank G Preston
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, Clinical Sciences Centre, University Hospital Aintree, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool, L9 7AL, UK
- Liverpool University Hospitals NHS Foundation Trust, Aintree Hospital, Liverpool, UK
| | - Jamie Burgess
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, Clinical Sciences Centre, University Hospital Aintree, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool, L9 7AL, UK
| | - Nicola Goodson
- Liverpool University Hospitals NHS Foundation Trust, Aintree Hospital, Liverpool, UK
- Research Institute for Sport and Exercise Science, Liverpool John Moores University, Liverpool, UK
| | - Nicholas Fallon
- Institute of Population Health, University of Liverpool, Liverpool, UK
| | - Bernhard Frank
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, Clinical Sciences Centre, University Hospital Aintree, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool, L9 7AL, UK
- The Walton Centre NHS Foundation Trust, Liverpool, UK
| | - Sizheng Steven Zhao
- Division of Musculoskeletal and Dermatological Science, School of Biological Sciences, Faculty of Biological Medicine and Health, Centre for Musculoskeletal Research, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
| | - Uazman Alam
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, Clinical Sciences Centre, University Hospital Aintree, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool, L9 7AL, UK.
- Centre for Biomechanics and Rehabilitation Technologies, Staffordshire University, Stoke-on-Trent, UK.
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Lautenbacher S, Horn-Hofmann C, Kunz M. Conditioned pain modulation: controlling for the order of baseline and conditioning. Pain 2025:00006396-990000000-00816. [PMID: 39907504 DOI: 10.1097/j.pain.0000000000003494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Accepted: 10/26/2024] [Indexed: 02/06/2025]
Abstract
ABSTRACT Conditioned pain modulation (CPM) is assumed to capture endogenous pain modulation. In standard CPM designs, the evaluation of a painful test stimulus (TS) (baseline) is followed by a second evaluation of the TS during/after application of a painful conditioning stimulus (CS) (treatment). However, these standard CPM within designs (baseline always preceding treatment) do not control for order effects, which might help to distinguish specific CPM inhibition from general habituation. To tackle this issue, we conducted 2 separate studies where we controlled for order effects to investigate whether CPM effects depend on the order of baseline and treatment. In both studies, a sample of 60 participants underwent 2 CPM test blocks: one standard order block (baseline before treatment) and one reversed order block (treatment before baseline), separated by a 20-minute break (randomized order across participants). Pain thresholds and pain ratings of phasic heat stimuli served as measures of TS. Cold water (study 1) and cuff pressure algometry (study 2) served as CS. We found significant CPM order effects in both studies and for both measures of TS (pain threshold and ratings). Only the standard CPM order (baseline before treatment) yielded robust pain inhibition effects, whereas the reversed order (treatment before baseline) led to no modulation or seeming pain facilitation. Because control for order effects is otherwise mandatory in within designs, it is surprising that it has been neglected in standard CPM protocols. Finding pain inhibition only in the standard CPM order suggests that CPM inhibition is at least partially confounded with habituation.
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Affiliation(s)
- Stefan Lautenbacher
- Physiological Psychology, Otto-Friedrich-University of Bamberg, Bamberg, Germany
- Bamberg Living Lab Dementia, BamLiD, Otto-Friedrich-University of Bamberg, Bamberg, Germany
| | - Claudia Horn-Hofmann
- Physiological Psychology, Otto-Friedrich-University of Bamberg, Bamberg, Germany
| | - Miriam Kunz
- Medical Psychology and Sociology, Faculty of Medicine, University of Augsburg, Augsburg, Germany
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Menéndez-Torre Á, Martin-Pintado-Zugasti A, Paris-Alemany A, Bocos-Corredor E, Molina-Álvarez M, Arribas-Romano A, Fernández-Carnero J. Pain sensitization and pain-related psychological factors in patients with temporomandibular disorders: an observational cross-sectional study. Clin Oral Investig 2024; 28:594. [PMID: 39400763 DOI: 10.1007/s00784-024-05954-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Accepted: 09/22/2024] [Indexed: 10/15/2024]
Abstract
BACKGROUND There is conflicting evidence on how central processing impairments affect patients with temporomandibular disorders (TMD). Moreover, there is sparse research on the assessment of endogenous pain modulation in this population through conditioned pain modulation (CPM) testing. OBJECTIVE(S) The main objective of this observational study was to evaluate the possible differences between myofascial TDM patients and healthy pain-free controls on psychophysical variables suggestive of central processing impairments (including temporal summation (TSP), pressure pain threshold (PPT) and conditioned pain modulation (CPM)). METHODS This is a cross-sectional observational study including a sample of patients with TMD and pain-free controls recruited from private and university clinics in Spain. Outcome measures included local and distal PPTs, temporal summation, conditioned pain modulation and psychological factors of depression, anxiety, kinesiophobia, fear avoidance beliefs and pain catastrophizing. RESULTS Fifty-nine patients with TMD of myofascial origin (32 years [IR: 25-43]) and 30 healthy, pain-free controls (29.5 years [IR: 25-41]) participated in the study and completed the evaluations. Patients with TMD showed significantly reduced CPM (p = 0.001; t = 3.31) and both local and distal PPTs (p < 0.05) when compared with controls, after adjusting for the influence of age and sex. TSP did not show any difference between the groups (p = 0.839; Z = 0.20). All psychological factors were higher in patients with TMD (p < 0.005), except for anxiety (p = 0.134). CONCLUSION Patients with myofascial TMD included in this study exhibited signs of altered central processing, linked to impaired descending pain modulation, distal hyperalgesia and psychological factors like depression, kinesiophobia, fear avoidance beliefs and pain catastrophizing but not anxiety.
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Affiliation(s)
- Ángela Menéndez-Torre
- Escuela Internacional de Doctorado, Department of Physical Therapy, Occupational Therapy, Rehabilitation and Physical Medicine, Universidad Rey Juan Carlos, Alcorcon, 28922, Spain
- Cognitive Neuroscience, Pain, and Rehabilitation Research Group (NECODOR), Faculty of Health Sciences, Rey Juan Carlos University, Madrid, Spain
- Servicio de Fisioterapia. Centro Médico Gava, Navalcarnero, Madrid, 28600, Spain
| | - Aitor Martin-Pintado-Zugasti
- Cognitive Neuroscience, Pain, and Rehabilitation Research Group (NECODOR), Faculty of Health Sciences, Rey Juan Carlos University, Madrid, Spain.
- Departamento de Fisioterapia, Facultad de Medicina, Universidad San Pablo-CEU, CEU Universities, Madrid, 28008, Spain.
| | - Alba Paris-Alemany
- Departamento de Radiología, Rehabilitación y Fisioterapia, Facultad de Enfermería, Fisioterapia y Podología, Universidad Complutense de Madrid, Madrid, 28040, Spain
- Motion in Brains Research Group, Centro Superior de Estudios Universitarios La Salle, Universidad Autónoma de Madrid, Aravaca, Madrid, 28023, Spain
- Instituto de Dolor Craneofacial y Neuromusculoesquelético (INDCRAN), Madrid, Spain
| | - Elena Bocos-Corredor
- Departamento de Fisioterapia, Facultad de Medicina, Universidad San Pablo-CEU, CEU Universities, Madrid, 28008, Spain
| | - Miguel Molina-Álvarez
- Escuela Internacional de Doctorado, Department of Physical Therapy, Occupational Therapy, Rehabilitation and Physical Medicine, Universidad Rey Juan Carlos, Alcorcon, 28922, Spain
- Cognitive Neuroscience, Pain, and Rehabilitation Research Group (NECODOR), Faculty of Health Sciences, Rey Juan Carlos University, Madrid, Spain
- Area of Pharmacology, Nutrition and Bromatology, Department of Basic Health Sciences, Universidad Rey Juan Carlos, Unidad Asociada I+D+i Instituto de Química Médica (IQM) CSIC-URJC, Madrid, Spain
| | - Alberto Arribas-Romano
- Escuela Internacional de Doctorado, Department of Physical Therapy, Occupational Therapy, Rehabilitation and Physical Medicine, Universidad Rey Juan Carlos, Alcorcon, 28922, Spain
- Cognitive Neuroscience, Pain, and Rehabilitation Research Group (NECODOR), Faculty of Health Sciences, Rey Juan Carlos University, Madrid, Spain
- Department of Physical and Occupational Therapy, Rehabilitation and Physical Medicine, Universidad Rey Juan Carlos, Madrid, 28922, Spain
| | - Josué Fernández-Carnero
- Cognitive Neuroscience, Pain, and Rehabilitation Research Group (NECODOR), Faculty of Health Sciences, Rey Juan Carlos University, Madrid, Spain
- Motion in Brains Research Group, Centro Superior de Estudios Universitarios La Salle, Universidad Autónoma de Madrid, Aravaca, Madrid, 28023, Spain
- Department of Physical and Occupational Therapy, Rehabilitation and Physical Medicine, Universidad Rey Juan Carlos, Madrid, 28922, Spain
- La Paz Hospital Institute for Health Research, IdiPAZ, Madrid, 28046, Spain
- Musculoskeletal Pain and Motor Control Research Group, Faculty of Sport Sciences, Universidad Europea de Madrid, Villaviciosa de Odón, 28670, Spain
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Irvine KA, Shi XY, Ferguson AR, Clark JD. Designer Receptor Exclusively Activated by Designer Drug (DREADD)-Mediated Activation of the Periaqueductal Gray Restores Nociceptive Descending Inhibition After Traumatic Brain Injury in Rats. J Neurotrauma 2024; 41:e1761-e1779. [PMID: 38588130 PMCID: PMC11386998 DOI: 10.1089/neu.2024.0031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/10/2024] Open
Abstract
Traumatic brain injury (TBI) patients frequently experience chronic pain that can enhance their suffering and significantly impair rehabilitative efforts. Clinical studies suggest that damage to the periaqueductal gray matter (PAG) following TBI, a principal center involved in endogenous pain control, may underlie the development of chronic pain. We hypothesized that TBI would diminish the usual pain control functions of the PAG, but that directly stimulating this center using a chemogenetic approach would restore descending pain modulation. We used a well-characterized lateral fluid percussion model (1.3 ± 0.1 atm) of TBI in male rats (n = 271) and measured hindpaw mechanical nociceptive withdrawal thresholds using von Frey filaments. To investigate the role of the PAG in pain both before and after TBI, we activated the neurons of the PAG using a Designer Receptor Exclusively Activated by Designer Drug (DREADD) viral construct. Immunohistochemical analysis of brain tissue was used to assess the location and confirm the appropriate expression of the viral constructs in the PAG. Activation of the PAG DREADD using clozapine N-oxide (CNO) caused hindpaw analgesia that could be blocked using opioid receptor antagonist, naloxone, in uninjured but not TBI rats. Due to the importance of descending serotonergic signaling in modulating nociception, we ablated spinal serotonin signaling using 5,7-DHT. This treatment strongly reduced CNO-mediated anti-nociceptive effects in TBI but not uninjured rats. To define the serotonergic receptor(s) required for the CNO-stimulated effects in TBI rats, we administered 5-HT7 (SB-269970) and 5-HT1A (WAY-100635) receptor antagonists but observed no effects. The selective 5-HT2A receptor antagonist ketanserin, however, blocked CNO's effects in the DREADD expressing TBI but not DREADD expressing sham TBI animals. Blockade of alpha-1 adrenergic receptors with prazosin also had no effect after TBI. Descending pain control originating in the PAG is mediated through opioid receptors in uninjured rats. TBI, however, fundamentally alters the descending nociceptive control circuitry such that serotonergic influences predominate, and those are mediated by the 5-HT2A receptor. These results provide further evidence that the PAG is a key target for anti-nociception after TBI.
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Affiliation(s)
- Karen-Amanda Irvine
- Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California, USA
- Anesthesiology Service Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA
| | - Xiao-You Shi
- Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California, USA
- Anesthesiology Service Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA
| | - Adam R Ferguson
- Brain and Spinal Injury Center, Department of Neurosurgery, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California, USA
- San Francisco Veterans Affairs Healthcare System, San Francisco, California, USA
| | - J David Clark
- Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California, USA
- Anesthesiology Service Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA
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Ang DC, Davuluri S, Kaplan S, Keefe F, Rini C, Miles C, Chen H. Duloxetine and cognitive behavioral therapy with phone-based support for the treatment of chronic musculoskeletal pain: study protocol of the PRECICE randomized control trial. Trials 2024; 25:330. [PMID: 38762720 PMCID: PMC11102257 DOI: 10.1186/s13063-024-08158-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 05/07/2024] [Indexed: 05/20/2024] Open
Abstract
BACKGROUND Chronic musculoskeletal pain (CMP) is the most common, disabling, and costly of all pain conditions. While evidence exists for the efficacy of both duloxetine and web-based cognitive behavioral therapy (CBT) as monotherapy, there is a clear need to consider study of treatment components that may complement each other. In addition, given the reported association between patient's adherence and treatment outcomes, strategies are needed to enhance participant's motivation to adopt and maintain continued use of newly learned pain coping skills from CBT. METHODS Two hundred eighty participants will be recruited from the primary care clinics of a large academic health care system in North Carolina. Participants with CMP will be randomized to one of three treatment arms: (1) combination treatment (duloxetine + web-based self-guided CBT) with phone-based motivational interviewing (MI), (2) combination treatment without phone-based MI, and (3) duloxetine monotherapy. Participants will be in the study for 24 weeks and will be assessed at baseline, week 13, and week 25. The primary outcome is the Brief Pain Inventory (BPI)-Global Pain Severity score, which combines BPI pain severity and BPI pain interference. Secondary measures include between-group comparisons in mean BPI pain severity and BPI pain interference scores. Data collection and outcome assessment will be blinded to treatment group assignment. DISCUSSION This randomized controlled trial (RCT) will determine if combination treatment with duloxetine and web-based CBT is superior to duloxetine monotherapy for the management of CMP. Furthermore, this RCT will determine the effectiveness of phone-based motivational interviewing in promoting the continued practice of pain coping skills, thereby enhancing treatment outcomes. TRIAL REGISTRATION NCT04395001 ClinicalTrials.gov. Registered on May 15, 2020.
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Affiliation(s)
- Dennis C Ang
- Department of Medicine/Rheumatology, Wake Forest University School of Medicine, Winston Salem, NC, 27157, USA.
| | - Swetha Davuluri
- Department of Psychiatry and Behavioral Medicine, Wake Forest University School of Medicine, Winston Salem, NC, USA
| | - Sebastian Kaplan
- Department of Psychiatry and Behavioral Medicine, Wake Forest University School of Medicine, Winston Salem, NC, USA
| | - Francis Keefe
- Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA
| | - Christine Rini
- Department of Medical Social Sciences, Northwestern University, Chicago, IL, USA
| | - Christopher Miles
- Department of Family Medicine, Wake Forest University School of Medicine, Winston Salem, NC, USA
| | - Haiying Chen
- Department of Biostatistical Sciences, Wake Forest University, Winston Salem, NC, USA
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Chen Q, Bharadwaj V, Irvine KA, Clark JD. Mechanisms and treatments of chronic pain after traumatic brain injury. Neurochem Int 2023; 171:105630. [PMID: 37865340 PMCID: PMC11790307 DOI: 10.1016/j.neuint.2023.105630] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 10/13/2023] [Accepted: 10/15/2023] [Indexed: 10/23/2023]
Abstract
While pain after trauma generally resolves, some trauma patients experience pain for months to years after injury. An example, relevant to both combat and civilian settings, is chronic pain after traumatic brain injury (TBI). Headache as well as pain in the back and extremities are common locations for TBI-related chronic pain to be experienced. TBI-related pain can exist alone or can exacerbate pain from other injuries long after healing has occurred. Consequences of chronic pain in these settings include increased suffering, higher levels of disability, serious emotional problems, and worsened cognitive deficits. The current review will examine recent evidence regarding dysfunction of endogenous pain modulatory mechanisms, neuroplastic changes in the trigeminal circuitry and alterations in spinal nociceptive processing as contributors to TBI-related chronic pain. Key pain modulatory centers including the locus coeruleus, periaqueductal grey matter, and rostroventromedial medulla are vulnerable to TBI. Both the rationales and existing evidence for the use of monoamine reuptake inhibitors, CGRP antagonists, CXCR2 chemokine receptor antagonists, and interventional therapies will be presented. While consensus guidelines for the management of chronic post-traumatic TBI-related pain are lacking, several approaches to this clinically challenging situation deserve focused evaluation and may prove to be viable therapeutic options.
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Affiliation(s)
- QiLiang Chen
- Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, School of Medicine, Stanford, CA, 94305, USA
| | - Vimala Bharadwaj
- Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, School of Medicine, Stanford, CA, 94305, USA
| | - Karen-Amanda Irvine
- Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, School of Medicine, Stanford, CA, 94305, USA; Anesthesiology Service, Veterans Affairs Palo Alto Health Care System, 3801 Miranda Ave (E4-220), Palo Alto, CA, 94304, USA
| | - J David Clark
- Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, School of Medicine, Stanford, CA, 94305, USA; Anesthesiology Service, Veterans Affairs Palo Alto Health Care System, 3801 Miranda Ave (E4-220), Palo Alto, CA, 94304, USA.
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Bossenger NR, Lewis GN, Rice DA, Shepherd D. The autonomic and nociceptive response to acute experimental stress is impaired in people with knee osteoarthritis: A preliminary study. NEUROBIOLOGY OF PAIN (CAMBRIDGE, MASS.) 2023; 14:100144. [PMID: 38099282 PMCID: PMC10719531 DOI: 10.1016/j.ynpai.2023.100144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Revised: 09/19/2023] [Accepted: 09/19/2023] [Indexed: 12/17/2023]
Abstract
Objective Alterations in autonomic function are evident in some chronic pain conditions but have not been thoroughly examined in people with osteoarthritis (OA). The study aimed to examine resting autonomic nervous system (ANS) function in people with knee OA, and the response of the autonomic and nociceptive systems to acute stress. Methods A preliminary cross-sectional study was undertaken involving people with knee OA (n = 14), fibromyalgia (n = 13), and pain-free controls (n = 15). The sympathetic and parasympathetic components of the ANS were assessed through measures of pre-ejection period (PEP), skin conductance level (SCL), and high frequency heart rate variability (HF HRV). The nociceptive system was assessed through pain ratings associated with a tonic heat pain stimulus. In separate sessions, ANS and heat pain measures were assessed at rest and in response to nociceptive and mental arithmetic stressors. Results The knee OA group showed reduced HF HRV at rest and reduced modulation in response to stress. Resting PEP and SCL were normal in the knee OA group but PEP modulation was impaired in both chronic pain groups during nociceptive stress. The expected reduction in tonic heat pain ratings in response to stress was lacking in the knee OA and FM groups. Conclusion Preliminary evidence shows impaired parasympathetic nervous system function at rest and in response to nociceptive and mental stress in people with knee OA, with some evidence of altered sympathetic nervous system function. Impaired ANS function could contribute to ongoing pain experienced, and interventions that target ANS function could be beneficial.
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Affiliation(s)
- Neil R Bossenger
- Health and Rehabilitation Research Institute, Auckland University of Technology, Auckland, New Zealand
| | - Gwyn N Lewis
- Health and Rehabilitation Research Institute, Auckland University of Technology, Auckland, New Zealand
| | - David A Rice
- Health and Rehabilitation Research Institute, Auckland University of Technology, Auckland, New Zealand
- Waitematā Pain Service, Te Whatu Ora Waitematā, Auckland, New Zealand
| | - Daniel Shepherd
- Department of Psychology, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland, New Zealand
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Amer-Cuenca JJ, Badenes-Ribera L, Biviá-Roig G, Arguisuelas MD, Suso-Martí L, Lisón JF. The dose-dependent effects of transcutaneous electrical nerve stimulation for pain relief in individuals with fibromyalgia: a systematic review and meta-analysis. Pain 2023; 164:1645-1657. [PMID: 36893318 DOI: 10.1097/j.pain.0000000000002876] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Accepted: 01/13/2023] [Indexed: 03/11/2023]
Abstract
ABSTRACT Transcutaneous electrical nerve stimulation (TENS) is a nonpharmacological modality widely used to manage pain; however, its effectiveness for individuals with fibromyalgia (FM) has been questioned. In previous studies and systematic reviews, variables related to dose of TENS application have not been considered. The objectives of this meta-analysis were (1) to determine the effect of TENS on pain in individuals with FM and (2) determine the dose-dependent effect of TENS dose parameters on pain relief in individuals with FM. We searched the PubMed, PEDro, Cochrane, and EMBASE databases for relevant manuscripts. Data were extracted from 11 of the 1575 studies. The quality of the studies was assessed using the PEDro scale and RoB-2 assessment. This meta-analysis was performed using a random-effects model that, when not considering the TENS dosage applied, showed that the treatment had no overall effect on pain (d+ = 0.51, P > 0.050, k = 14). However, the moderator analyses, which were performed assuming a mixed-effect model, revealed that 3 of the categorical variables were significantly associated with effect sizes: the number of sessions ( P = 0.005), the frequency ( P = 0.014), and the intensity ( P = 0.047). The electrode placement was not significantly associated with any effect sizes. Thus, there is evidence that TENS can effectively reduce pain in individuals with FM when applied at high or at mixed frequencies, a high intensity, or in long-term interventions involving 10 or more sessions. This review protocol was registered at PROSPERO (CRD42021252113).
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Affiliation(s)
- Juan J Amer-Cuenca
- Department of Nursing and Physiotherapy, Universidad Cardenal Herrera-CEU, CEU Universities, Spain
| | - Laura Badenes-Ribera
- Department of Behavioral Sciences Methodology, University of Valencia, Valencia, Spain
| | - Gemma Biviá-Roig
- Department of Nursing and Physiotherapy, Universidad Cardenal Herrera-CEU, CEU Universities, Spain
| | - María D Arguisuelas
- Department of Nursing and Physiotherapy, Universidad Cardenal Herrera-CEU, CEU Universities, Spain
| | - Luis Suso-Martí
- Department of Nursing and Physiotherapy, Universidad Cardenal Herrera-CEU, CEU Universities, Spain
| | - Juan F Lisón
- Department of Biomedical Sciences, Universidad Cardenal Herrera-CEU, CEU Universities, Spain
- CIBEROBN, ISCIII, Madrid, Spain
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10
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DuPont CM, Olmstead R, Reid MJ, Hamilton KR, Campbell CM, Finan PH, Sadeghi N, Castillo D, Irwin MR, Smith MT. A randomized, placebo-controlled, double-blinded mechanistic clinical trial using endotoxin to evaluate the relationship between insomnia, inflammation, and affective disturbance on pain in older adults: A protocol for the sleep and Healthy Aging Research for pain (SHARE-P) study. Brain Behav Immun Health 2023; 30:100642. [PMID: 37256193 PMCID: PMC10225887 DOI: 10.1016/j.bbih.2023.100642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 05/18/2023] [Indexed: 06/01/2023] Open
Abstract
UNLABELLED Chronic pain is prevalent in older adults. Treatment, especially with opioids, is often ineffective and poses considerable negative consequences in this population. To improve treatment, it is important to understand why older adults are at a heightened risk for developing chronic pain. Insomnia is a major modifiable risk factor for chronic pain that is ubiquitous among older adults. Insomnia can also lead to heightened systemic inflammation and affective disturbance, both of which may further exacerbate pain conditions in older adults. Endotoxin exposure can be used as an experimental model of systemic inflammation and affective disturbance. The current study aims to understand how insomnia status and endotoxin-induced changes in inflammation and affect (increased negative affect and decreased positive affect) may interact to impact pain facilitatory and inhibitory processes in older adults. Longitudinal data will also assess how pain processing, affective, and inflammatory responses to endotoxin may predict the development of pain and/or depressive symptoms. The current study is a randomized, double-blinded, placebo-controlled, mechanistic clinical trial in men and women, with and without insomnia, aged 50 years and older. Participants were randomized to either 0.8ng/kg endotoxin injection or saline placebo injection. Daily diaries were used to collect variables related to sleep, mood, and pain at two-week intervals during baseline and 3-, 6-, 9-, and 12-months post-injection. Primary outcomes during the experimental phase include conditioned pain modulation, temporal summation, and affective pain modulation ∼5.5 hours after injection. Primary outcomes for longitudinal assessments are self-reported pain intensity and depressive symptoms. The current study uses endotoxin as an experimental model for pain. In doing so, it aims to extend the current literature by: (1) including older adults, (2) investigating insomnia as a potential risk factor for chronic pain, (3) evaluating the role of endotoxin-induced affective disturbances on pain sensitivity, and (4) assessing sex differences in endotoxin-induced hyperalgesia. CLINICALTRIALSGOV NCT03256760. TRIAL SPONSOR NIH R01AG057750-01.
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Affiliation(s)
- Caitlin M. DuPont
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, School of Medicine, Baltimore, MD, USA
| | - Richard Olmstead
- Department of Psychiatry and Biobehavioral Sciences, Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA, USA
| | - Matthew J. Reid
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, School of Medicine, Baltimore, MD, USA
| | - Katrina R. Hamilton
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, School of Medicine, Baltimore, MD, USA
| | - Claudia M. Campbell
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, School of Medicine, Baltimore, MD, USA
| | - Patrick H. Finan
- University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Nina Sadeghi
- Department of Psychiatry and Biobehavioral Sciences, Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA, USA
| | - Daisy Castillo
- Department of Psychiatry and Biobehavioral Sciences, Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA, USA
| | - Michael R. Irwin
- Department of Psychiatry and Biobehavioral Sciences, Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA, USA
| | - Michael T. Smith
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, School of Medicine, Baltimore, MD, USA
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11
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Song Y, Kirsch G, Jarjour W. The Utility of Ultrasound in Evaluating Joint Pain in Systemic Lupus Erythematosus: Looking beyond Fibromyalgia. J Pers Med 2023; 13:jpm13050763. [PMID: 37240932 DOI: 10.3390/jpm13050763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 04/26/2023] [Accepted: 04/27/2023] [Indexed: 05/28/2023] Open
Abstract
BACKGROUND Systemic lupus erythematosus (SLE) is a complex autoimmune condition with varied clinical presentations, and musculoskeletal pain is one of the most commonly associated symptoms. However, fibromyalgia (FM) is a prevalent co-existing condition in SLE patients that can also cause widespread pain, and in patients with both conditions, it is often difficult to distinguish the underlying cause of musculoskeletal pain and provide optimal therapy. METHODS A retrospective cohort study was conducted including all adult SLE patients who received musculoskeletal ultrasound (US) examinations for joint pain at the Ohio State University Wexner Medical Center between 1 July 2012, and 30 June 2022. Binary and multiple logistic regression analyses were performed to determine predictors of US-detected inflammatory arthritis as well as improved musculoskeletal pain. RESULTS A total of 31 of 72 SLE patients (43.1%) had a co-existing diagnosis of FM. In binary logistic regression, a co-existing diagnosis of FM was not significantly associated with US-detected inflammatory arthritis. In multiple logistic regression analysis, clinically detected synovitis was significantly associated with US-detected inflammatory arthritis (aOR, 142.35, p < 0.01), and there was also a weak association with erythrocyte sedimentation rate (ESR) (aOR 1.04, p = 0.05). In separate multiple logistic regression analysis, US-guided intra-articular steroid injection was the only predictor of improved joint pain at follow-up visit (aOR 18.43, p < 0.001). CONCLUSIONS Musculoskeletal US can be an effective modality to detect inflammatory arthritis as well as to guide targeted intra-articular steroid injection to alleviate joint pain in SLE patients with or without FM.
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Affiliation(s)
- Yeohan Song
- Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
- Division of Rheumatology and Immunology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Gabriel Kirsch
- Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Wael Jarjour
- Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
- Division of Rheumatology and Immunology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
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12
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Staud R, Godfrey MM, Riley JL, Fillingim RB. Efficiency of pain inhibition and facilitation of fibromyalgia patients is not different from healthy controls: Relevance of sensitivity-adjusted test stimuli. Br J Pain 2023; 17:182-194. [PMID: 37057258 PMCID: PMC10088420 DOI: 10.1177/20494637221138318] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background Pain is a dynamic phenomenon dependent on the balance of endogenous excitatory and inhibitory systems, which can be characterized by quantitative sensory testing. Many previous studies of pain modulatory capacity of patients with fibromyalgia syndrome (FM) have reported decreased pain inhibition or increased pain facilitation. This is the first study to assess pain modulation, including conditioned pain modulation (CPM) and temporal pain summation, in the same healthy control (HC) and FM participants. Methods Only sensitivity-adjusted stimuli were utilized for testing of conditioned pain modulation (CPM) and temporal pain summation in 23 FM patients and 28 HC. All subjects received sensitivity-adjusted ramp-hold (sRH) during testing of pain facilitation (temporal summation) and pain inhibition (CPM). CPM efficacy was evaluated with test stimuli applied either concurrently or after application of the conditioning stimulus. Finally, the effects of CPM on pressure pain thresholds were tested. Results FM subjects required significantly less intense test and conditioning stimuli than HC participants to achieve standardized pain ratings of 50 ± 10 numerical rating scale (NRS) (p = 0.03). Using such stimuli, FM subjects' temporal pain summation and CPM efficacy was not significantly different from HC (all p > 0.05), suggesting similar pain facilitation and inhibition. Furthermore, the CPM efficacy of FM and HC participants was similar regardless of whether the test stimuli were applied during or after the conditioning stimulus (p > 0.05). Conclusion Similar to previous studies, FM participants demonstrated hyperalgesia to heat, cold, and mechanical stimuli. However, using only sensitivity-adjusted stimuli during CPM and temporal summation testing, FM patients demonstrated similarly effective pain inhibition and facilitation than HC, suggesting that their pain modulation is not abnormal.
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Affiliation(s)
- Roland Staud
- Department of Medicine, University of Florida, Gainesville, FL, USA
| | | | - Joseph L Riley
- College of Dentistry, University of Florida, Gainesville, FL, USA
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13
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Kourbanova K, Alexandre C, Latremoliere A. Effect of sleep loss on pain-New conceptual and mechanistic avenues. Front Neurosci 2022; 16:1009902. [PMID: 36605555 PMCID: PMC9807925 DOI: 10.3389/fnins.2022.1009902] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Accepted: 11/29/2022] [Indexed: 12/24/2022] Open
Abstract
Introduction Sleep disturbances increase pain sensitivity in clinical and preclinical settings, but the precise mechanisms are unknown. This represents a major public health issue because of the growing sleep deficiency epidemic fueled by modern lifestyle. To understand the neural pathways at the intersection between sleep and pain processes, it is critical to determine the precise nature of the sleep disruptions that increase pain and the specific component of the pain response that is targeted. Methods We performed a review of the literature about sleep disturbances and pain sensitivity in humans and rodents by taking into consideration the targeted sleep stage (REMS, non-NREMS, or both), the amount of sleep lost, and the different types of sleep disruptions (partial or total sleep loss, duration, sleep fragmentation or interruptions), and how these differences might affect distinct components of the pain response. Results We find that the effects of sleep disturbances on pain are highly conserved among species. The major driver for pain hypersensitivity appears to be the total amount of sleep lost, while REMS loss by itself does not seem to have a direct effect on pain sensitivity. Sleep loss caused by extended wakefulness preferentially increases pain perception, whereas interrupted and limited sleep strongly dysregulates descending controls such as DNIC, especially in women. Discussion We discuss the possible mechanisms involved, including an increase in inflammatory processes, a loss of nociceptive inhibitory pathways, and a defect in the cognitive processing of noxious input.
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Affiliation(s)
- Kamila Kourbanova
- Department of Neurosurgery, Neurosurgery Pain Research Institute, Johns Hopkins School of Medicine, Baltimore, MD, United States
- Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, United States
| | - Chloe Alexandre
- Department of Neurosurgery, Neurosurgery Pain Research Institute, Johns Hopkins School of Medicine, Baltimore, MD, United States
- Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, United States
| | - Alban Latremoliere
- Department of Neurosurgery, Neurosurgery Pain Research Institute, Johns Hopkins School of Medicine, Baltimore, MD, United States
- Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, United States
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14
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Stress-induced hyperalgesia instead of analgesia in patients with chronic musculoskeletal pain. NEUROBIOLOGY OF PAIN (CAMBRIDGE, MASS.) 2022; 13:100110. [PMID: 36561877 PMCID: PMC9764253 DOI: 10.1016/j.ynpai.2022.100110] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 11/21/2022] [Accepted: 12/04/2022] [Indexed: 12/12/2022]
Abstract
Many individuals with chronic musculoskeletal pain (CMP) show impairments in their pain-modulatory capacity. Although stress plays an important role in chronic pain, it is not known if stress-induced analgesia (SIA) is affected in patients with CMP. We investigated SIA in 22 patients with CMP and 18 pain-free participants. Pain thresholds, pain tolerance and suprathreshold pain ratings were examined before and after a cognitive stressor that typically induces pain reduction (SIA). Whereas the controls displayed a significant increase in pain threshold in response to the stressor, the patients with CMP showed no analgesia. In addition, increased pain intensity ratings after the stressor indicated hyperalgesia (SIH) in the patients with CMP compared to controls. An exploratory analysis showed no significant association of SIA or SIH with spatial pain extent. We did not observe significant changes in pain tolerance or pain unpleasantness ratings after the stressor in patients with CMP or controls. Our data suggest that altered stress-induced pain modulation is an important mechanism involved in CMP. Future studies need to clarify the psychobiological mechanisms of these stress-induced alterations in pain processing and determine the role of contributing factors such as early childhood trauma, catastrophizing, comorbidity with mental disorders and genetic predisposition.
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15
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de la Coba P, Montoro CI, Reyes Del Paso GA, Galvez-Sánchez CM. Algometry for the assessment of central sensitisation to pain in fibromyalgia patients: a systematic review. Ann Med 2022; 54:1403-1422. [PMID: 35579545 PMCID: PMC9122375 DOI: 10.1080/07853890.2022.2075560] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
INTRODUCTION The pathophysiology of fibromyalgia (FM) is related to central sensitisation (CS) to pain. Algometry allows assessing CS based on dynamic evoked pain. However, current algometrýs protocols require optimising, unifying and updating. OBJECTIVES 1) identify the dynamic pain measures used most frequently to effectively assess CS processes in FM, and 2) consider the future of the algometry assessing CS in these patients. METHODS Cochrane Collaboration guidelines and PRISMA statements were followed. The protocol was registered in PROSPERO database (ID: CRD42021270135). The selected articles were evaluated using the Cochrane risk of bias (ROB) assessment tool. The PubMed, Scopus, and Web of Science databases were searched. RESULTS Thirty-four studies were selected, including measures such as temporal summation of pain (TSP), aftersensations (AS), spatial summation of pain (SSP), the noxious flexion reflex (NFR) threshold, conditioned pain modulation (CPM), cutaneous silent period (CuSP), and slowly repeated evoked pain (SREP); and evoked pain combined with neuroimaging. Each measure offered various advantages and limitations. According to ROB, 28 studies were of low quality, 3 of moderate quality, and 3 of high quality. CONCLUSIONS Several pain indicators have been demonstrated to successfully examine CS involvement in FM in the last years. Algometry, especially when it involves diverse body sites and tissues, might provide further insight into (1) the evaluation of psychological factors known to influence pain experience, (2) new dynamic pain indicators, and (3) the simultaneous use of certain neuroimaging techniques. Further research clarifying the mechanisms underlying some of these measures, and homogenisation and optimisation of the algometrýs protocols, are needed. KEY MESSAGESAlgometry allows for assessing Central Sensitisation by applying dynamic evoked pain.The future of algometry could relapse in its combination with neuroimaging.Recently-emerged pain indicators should be considered for algometrýs new protocols.
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16
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Christensen SWM, Almsborg, M. H, Vain, M. TS, Vaegter HB. The Effect of Virtual Reality on Cold Pain Sensitivity in Patients with Fibromyalgia and Pain-Free Individuals: A Randomized Crossover Study. Games Health J 2022. [DOI: 10.1089/g4h.2022.0138] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Affiliation(s)
- Steffan Wittrup McPhee Christensen
- Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
- Department of Physiotherapy, University College of Northern Denmark, Aalborg, Denmark
| | - Heidi Almsborg, M.
- Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
- Multidisciplinary Pain Center Naestved, Naestved Hospital, Naestved, Denmark
| | - Thomas Søgaard Vain, M.
- Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
- Smertefys.nu, Physiotherapy Clinic, Copenhagen, Denmark
| | - Henrik Bjarke Vaegter
- Pain Research Group, Pain Center, Department of Anesthesiology and Intensive Care Medicine, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
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Büchel C. Pain persistence and the pain modulatory system: an evolutionary mismatch perspective. Pain 2022; 163:1274-1276. [PMID: 34855646 PMCID: PMC7612894 DOI: 10.1097/j.pain.0000000000002522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Accepted: 10/13/2021] [Indexed: 11/26/2022]
Affiliation(s)
- Christian Büchel
- Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
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18
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Peterson JA, Bemben MG, Larson RD, Pereira H, Crowson HM, Black CD. Symptomatic but not Asymptomatic COVID-19 Impairs Conditioned Pain Modulation in Young Adults. THE JOURNAL OF PAIN 2022; 23:1923-1932. [PMID: 35872293 PMCID: PMC9303070 DOI: 10.1016/j.jpain.2022.06.010] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 06/07/2022] [Accepted: 06/15/2022] [Indexed: 01/08/2023]
Abstract
Pain is a common symptom reported in COVID-19 patients. Impaired endogenous pain-modulatory mechanisms such as conditioned pain modulation (CPM), and exercise-induced hypoalgesia (EIH) have been found in chronic pain conditions but is often overlooked in acute conditions that evoke painful symptoms, such as COVID-19. The purpose was to compare pressure-pain sensitivity, CPM, and EIH function among individuals who previously had COVID-19, both symptomatically and asymptomatically, and a healthy control group. Pressure pain thresholds of 59 participants were assessed in the forearm and leg using a pressure algometer before and after 1) submersion of their dominant foot in cold water (2°C) for 1min; and 2) isometric knee extension performed to task-failure at 25% of their maximal contraction. The CPM response was attenuated in individuals who were infected with symptomatic COVID-19 (N = 26) compared to asymptomatic COVID-19 (N = 13) in arm (-1.0% ± 20.3 vs 33.3% ± 26.2; P < .001) and leg (12.8% ± 22.0 vs 33.8% ± 28.2; P = .014) and compared to controls (N = 20) in arm only (-1.0% ± 26.2 vs 23.4% ± 28.2; P = .004). The EIH response was not different between groups. CPM was impaired in individuals who had symptomatic COVID-19, which may have long-term implications on pain modulation. Perspective This study reveals that CPM was impaired in individuals who had symptomatic COVID-19 during the first wave of COVID-19, pre vaccine. These findings present a preliminary motive to study the long-term implications of COVID-19 and its effects on pain modulation.
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19
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Irvine KA, Peters CM, Vazey EM, Ferguson AR, Clark JD. Activation of the Locus Coeruleus Mediated by Designer Receptor Exclusively Activated by Designer Drug Restores Descending Nociceptive Inhibition after Traumatic Brain Injury in Rats. J Neurotrauma 2022; 39:964-978. [PMID: 35412843 PMCID: PMC9467637 DOI: 10.1089/neu.2021.0485] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Disruption of endogenous pain control mechanisms including descending pain inhibition has been linked to several forms of pain including chronic pain after traumatic brain injury (TBI). The locus coeruleus (LC) is the principal noradrenergic (NA) nucleus participating in descending pain inhibition. We therefore hypothesized that selectively stimulating LC neurons would reduce nociception after TBI. All experiments used a well-characterized rat lateral fluid percussion model of TBI. NA neurons were stimulated by administering clozapine N-oxide (CNO) to rats selectively expressing a designer receptor exclusively activated by designer drug (DREADD) viral construct in their LC's. Mechanical nociceptive thresholds were measured using von Frey fibers. The efficacy of diffuse noxious inhibitory control (DNIC), a critical endogenous pain control mechanism, was assessed using the hindpaw administration of capsaicin. Immunohistochemical analyses demonstrated the selective expression of the DREADD construct in LC neurons after stereotactic injection. During the 1st week after TBI, when rats demonstrated hindlimb (HL) nociceptive sensitization, CNO administration provided transient anti-allodynia in DREADD-expressing rats but not in rats injected with control virus. Seven weeks after TBI we observed a complete loss of DNIC in response to capsaicin. However, CNO administration largely restored DNIC in TBI DREADD-expressing rats but not those injected with control virus. Unexpectedly, the effects of LC activation in the DREADD-expressing rats were blocked by the α-1 adrenergic receptor antagonist prazosin, but not the α-2 adrenergic receptor antagonist atipamezole. These results suggest that directly stimulating the LC after TBI can reduce both early and late manifestations of dysfunctional endogenous pain regulation. Clinical approaches to activating descending pain circuits may reduce suffering in those with pain after TBI.
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Affiliation(s)
- Karen-Amanda Irvine
- Department of Anesthesiology, Perioperative and Pain Medicine; Stanford University, School of Medicine, Stanford, California, USA.,Anesthesiology Service; Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA.,Address correspondence to: Karen-Amanda Irvine, PhD, Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, School of Medicine, Stanford, CA 94305, USA
| | - Christopher M. Peters
- Department of Anesthesiology, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA
| | - Elena M. Vazey
- Department of Biology, University of Massachusetts Amherst, Amherst Massachusetts, USA
| | - Adam R. Ferguson
- University of California San Francisco, Brain and Spinal Injury Center, Department of Neurosurgery, San Francisco, California, USA
| | - J. David Clark
- Department of Anesthesiology, Perioperative and Pain Medicine; Stanford University, School of Medicine, Stanford, California, USA.,Anesthesiology Service; Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA
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Pergolizzi J, Magnusson P, Coluzzi F, Breve F, LeQuang JAK, Varrassi G. Multimechanistic Single-Entity Combinations for Chronic Pain Control: A Narrative Review. Cureus 2022; 14:e26000. [PMID: 35855248 PMCID: PMC9286298 DOI: 10.7759/cureus.26000] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Accepted: 06/15/2022] [Indexed: 11/05/2022] Open
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21
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Güereca YM, Kell PA, Kuhn BL, Hellman N, Sturycz CA, Toledo TA, Huber FA, Demuth M, Lannon EW, Palit S, Shadlow JO, Rhudy JL. The Relationship Between Experienced Discrimination and Pronociceptive Processes in Native Americans: Results From the Oklahoma Study of Native American Pain Risk. THE JOURNAL OF PAIN 2022; 23:1006-1024. [PMID: 35021117 DOI: 10.1016/j.jpain.2021.12.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 11/30/2021] [Accepted: 12/20/2021] [Indexed: 12/24/2022]
Abstract
Native Americans (NAs) have higher pain rates than the general U.S. population. It has been found that increased central sensitization and reduced pain inhibition are pronociceptive processes that increase pain risk; yet, little attention has focused on the influence of psychosocial factors. Discrimination is a psychosocial factor associated with increased pain in other minoritized groups; however, it is unclear whether it also promotes pain in NAs. This study analyzed data from 269 healthy, pain-free participants (N = 134 non-Hispanic whites [NHWs], N = 135 NAs) from the Oklahoma Study of Native American Pain Risk. Experienced discrimination was measured using the Everyday Discrimination Scale (EDS). Nociceptive processes were measured via static measures of spinal sensitivity (nociceptive flexion reflex [NFR] threshold, 3-stimulation NFR threshold), temporal summation of pain (TS-Pain) and nociceptive flexion reflex (TS-NFR), and conditioned pain modulation of pain (CPM-Pain) and NFR (CPM-NFR). Results demonstrated that greater discrimination was associated with enhanced TS-NFR and impaired CPM-NFR but not static measures of spinal sensitivity or measures of pain modulation (TS-Pain, CPM-Pain). Although the effects of discrimination on outcomes were similar in both groups (not moderated by ethnicity), NAs experienced higher levels of discrimination and therefore discrimination mediated a relationship between ethnicity and impaired CPM-NFR. This indicates experienced discrimination may promote a pain risk phenotype in NAs that involves spinal sensitization resulting from impaired inhibition of spinal nociception without sensitization of pain experience. PERSPECTIVE: This study found that discrimination was associated with spinal sensitization and impaired descending inhibition of spinal nociception. These findings bolster our understanding of how social stressors experienced disproportionately by minoritized groups can contribute to pain outcomes.
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Affiliation(s)
- Yvette M Güereca
- Department of Psychology, The University of Tulsa, Tulsa, Oklahoma
| | - Parker A Kell
- Department of Psychology, The University of Tulsa, Tulsa, Oklahoma
| | - Bethany L Kuhn
- Department of Psychology, The University of Tulsa, Tulsa, Oklahoma
| | - Natalie Hellman
- Department of Psychology, The University of Tulsa, Tulsa, Oklahoma
| | | | - Tyler A Toledo
- Department of Psychology, The University of Tulsa, Tulsa, Oklahoma
| | | | - Mara Demuth
- Department of Psychology, The University of Tulsa, Tulsa, Oklahoma
| | - Edward W Lannon
- Department of Psychology, The University of Tulsa, Tulsa, Oklahoma
| | - Shreela Palit
- University of Florida, Pain Research and Intervention Center of Excellence, Gainesville, Florida
| | - Joanna O Shadlow
- Department of Psychology, The University of Tulsa, Tulsa, Oklahoma
| | - Jamie L Rhudy
- Department of Psychology, The University of Tulsa, Tulsa, Oklahoma.
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22
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de Oliveira Franco Á, da Silveira Alves CF, Vicuña P, Bandeira J, de Aratanha MA, Torres ILS, Fregni F, Caumo W. Hyper-connectivity between the left motor cortex and prefrontal cortex is associated with the severity of dysfunction of the descending pain modulatory system in fibromyalgia. PLoS One 2022; 17:e0247629. [PMID: 35622879 PMCID: PMC9140239 DOI: 10.1371/journal.pone.0247629] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 03/20/2022] [Indexed: 12/30/2022] Open
Abstract
INTRODUCTION The association between descending pain modulatory system (DPMS) dysfunction and fibromyalgia has been previously described, but more studies are required on its relationship with aberrant functional connectivity (FC) between the motor and prefrontal cortices. OBJECTIVES The objective of this cross-sectional observational study was to compare the intra- and interhemispheric FC between the bilateral motor and prefrontal cortices in women with fibromyalgia, comparing responders and nonresponders to the conditioned pain modulation (CPM) test. METHODS A cross-sectional sample of 37 women (23 responders and 14 nonresponders to the CPM test) with fibromyalgia diagnosed according to the American College of Rheumatology criteria underwent a standardized clinical assessment and an FC analysis using functional near-infrared spectroscopy. DPMS function was inferred through responses to the CPM test, which were induced by hand immersion in cold water (0-1°C). A multivariate analysis of covariance for main effects between responders and nonresponders was conducted using the diagnosis of multiple psychiatric disorders and the use of opioid and nonopioid analgesics as covariates. In addition, we analyzed the interaction between the CPM test response and the presence of multiple psychiatric diagnoses. RESULTS Nonresponders showed increased FC between the left motor cortex (lMC) and the left prefrontal cortex (lPFC) (t = -2.476, p = 0.01) and right prefrontal cortex (rPFC) (t = -2.363, p = 0.02), even when both were considered as covariates in the regression analysis (lMC-lPFC: β = -0.127, t = -2.425, p = 0.021; lMC-rPFC: β = -0.122, t = -2.222, p = 0.033). Regarding main effects, a significant difference was only observed for lMC-lPFC (p = 0.035). A significant interaction was observed between the psychiatric disorders and nonresponse to the CPM test in lMC-lPFC (β = -0.222, t = -2.275, p = 0.03) and lMC-rPFC (β = -0.211, t = -2.2, p = 0.035). Additionally, a significant interaction was observed between the CPM test and FC in these two region-of-interest combinations, despite the psychiatric diagnoses (lMC-lPFC: β = -0.516, t = -2.447, p = 0.02; lMC-rPFC: β = -0.582, t = -2.805, p = 0.008). CONCLUSIONS Higher FC between the lMC and the bilateral PFC may be a neural marker of DPMS dysfunction in women with fibromyalgia, although its interplay with psychiatric diagnoses also seems to influence this association.
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Affiliation(s)
- Álvaro de Oliveira Franco
- Laboratory of Pain and Neuromodulation, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
| | - Camila Fernanda da Silveira Alves
- Laboratory of Pain and Neuromodulation, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
- Postgraduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Paul Vicuña
- Laboratory of Pain and Neuromodulation, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
- Postgraduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Janete Bandeira
- Postgraduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | | | - Iraci L. S. Torres
- Postgraduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
- Translational Nucleus: Pain Pharmacology and Neuromodulation, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
| | - Felipe Fregni
- Laboratory of Neuromodulation and Center for Clinical Research Learning, Physics and Rehabilitation Department, Spaulding Rehabilitation Hospital, Boston, MA, United States of America
| | - Wolnei Caumo
- Laboratory of Pain and Neuromodulation, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
- Postgraduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
- Pain and Palliative Care Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
- Department of Surgery, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
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Sensory Thresholds and Peripheral Nerve Responses in Chronic Tension-Type Headache and Neuropsychological Correlation. J Clin Med 2022; 11:jcm11071905. [PMID: 35407512 PMCID: PMC8999240 DOI: 10.3390/jcm11071905] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Revised: 03/25/2022] [Accepted: 03/27/2022] [Indexed: 02/06/2023] Open
Abstract
Chronic tension-type headache (CTTH) is a common disease with no fully defined pathophysiological processes. We designed a study to value electrophysiological responses in these patients and their correlation with possible psychopathological manifestations in order to deepen understanding of central and peripheral mechanisms of CTTH. In 40 patients with CTTH and 40 healthy controls, we used electrical stimulation to determine sensory threshold (SPT) and pain perception threshold (PPT) and the characteristics of the electrophysiological sensory nerve action potential (SNAP): initial sensory response (ISR) and supramaximal response (SMR). We then calculated the intensity differences between thresholds (IDT), namely SPT-PPT, ISR-SMR and SMR-PPT, and correlated these IDTs with psychological characteristics: trait and state anxiety, depression, and emotional regulation. The SPT, together with the ISR and SMR thresholds, were higher (p < 0.01) in CTTH patients. The SMR-PPT IDT was smaller and correlated with significantly higher indicators of depression, state and trait anxiety, and poorer cognitive reappraisal. CTTH patients have less capacity to recognize non-nociceptive sensory stimuli, greater tendency toward pain facilitation, and a poor central pain control requiring higher stimulation intensity thresholds to reach the start and the peak amplitude of the SNAP. This is consistent with relative hypoexcitability of the Aβ nerve fibers in distant regions from the site of pain, and therefore, it could be considered a generalized dysfunction with a focal expression. Pain facilitation is directly associated with psychological comorbidity.
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Oliva V, Gregory R, Brooks JC, Pickering AE. Central pain modulatory mechanisms of attentional analgesia are preserved in fibromyalgia. Pain 2022; 163:125-136. [PMID: 33941755 PMCID: PMC8675057 DOI: 10.1097/j.pain.0000000000002319] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 03/06/2021] [Accepted: 03/11/2021] [Indexed: 11/25/2022]
Abstract
ABSTRACT Fibromyalgia is a prevalent pain condition that is associated with cognitive impairments including in attention, memory, and executive processing. It has been proposed that fibromyalgia may be caused by altered central pain processing characterised by a loss of endogenous pain modulation. We tested whether attentional analgesia, where cognitive engagement diminishes pain percept, was attenuated in patients with fibromyalgia (n = 20) compared with matched healthy controls (n = 20). An individually calibrated, attentional analgesia paradigm with a 2 × 2 factorial design was used with brain and brainstem-focussed functional magnetic resonance imaging. Patients with fibromyalgia had both lower heat pain thresholds and speeds in a visual attention task. When this was taken into account for both attentional task and thermal stimulation, both groups exhibited an equivalent degree of attentional analgesia. Functional magnetic resonance imaging analysis showed similar patterns of activation in the main effects of pain and attention in the brain and brainstem (with the sole exceptions of increased activation in the control group in the frontopolar cortex and the ipsilateral locus coeruleus). The attentional analgesic effect correlated with activity in the periaqueductal gray and rostral ventromedial medulla. These findings indicate that patients with fibromyalgia can engage the descending pain modulatory system if the attentional task and noxious stimulus intensity are appropriately titrated.
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Affiliation(s)
- Valeria Oliva
- School of Physiology, Pharmacology & Neuroscience, University of Bristol, Bristol, United Kingdom
| | - Robert Gregory
- School of Physiology, Pharmacology & Neuroscience, University of Bristol, Bristol, United Kingdom
- Anaesthesia, Pain & Critical Care Sciences, Bristol Medical School, University Hospitals Bristol, Bristol, United Kingdom
| | - Jonathan C.W. Brooks
- School of Psychological Science, University of Bristol, Bristol, United Kingdom
- University of East Anglia Brain Imaging Centre, School of Psychology, Norwich, United Kingdom
| | - Anthony E. Pickering
- School of Physiology, Pharmacology & Neuroscience, University of Bristol, Bristol, United Kingdom
- Anaesthesia, Pain & Critical Care Sciences, Bristol Medical School, University Hospitals Bristol, Bristol, United Kingdom
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25
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Augière T, Desjardins A, Paquette Raynard E, Brun C, Pinard AM, Simoneau M, Mercier C. Tactile Detection in Fibromyalgia: A Systematic Review and a Meta-Analysis. FRONTIERS IN PAIN RESEARCH 2021; 2:740897. [PMID: 35295451 PMCID: PMC8915638 DOI: 10.3389/fpain.2021.740897] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Accepted: 11/29/2021] [Indexed: 11/24/2022] Open
Abstract
Fibromyalgia is a chronic pain syndrome characterized by sensorimotor deficits and distortions of body representation, that could both be caused by alterations in sensory processing. Several studies suggest a hypersensitivity to various sensory stimulations in fibromyalgia but results on detection of both noxious and non-noxious tactile stimulation, which are particularly relevant for body representation and motor control, remain conflicting. Therefore, the aim of this study is to systematically review and quantify the detection thresholds to noxious and non-noxious tactile stimuli in individuals with fibromyalgia compared to pain-free controls. A systematic review and a meta-analysis were performed in the MEDLINE, EMBASE, CINAHL, Cochrane, PsycInfo and Web of Science databases using keywords related to fibromyalgia, tactile pain detection threshold, tactile detection threshold and quantitative sensory testing. Nineteen studies were included in the review, with 12 in the meta-analysis. Despite the heterogeneity of the results, the data from both the review and from the meta-analysis suggest a trend toward hyperalgesia and no difference of sensitivity to non-noxious tactile stimuli in participants with fibromyalgia compared to healthy controls. This contradicts the hypothesis of a general increase in responsiveness of the central nervous system to noxious and non-noxious stimulations in fibromyalgia. This study shows no alteration of the sensitivity to non-noxious tactile stimulation in fibromyalgia, suggesting that an altered unimodal processing is not sufficient to explain symptoms such as sensorimotor impairments and body representation distortions. Future research should investigate whether alterations in multisensory integration could contribute to these symptoms.
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Affiliation(s)
- Tania Augière
- Center for Interdisciplinary Research in Rehabilitation and Social Integration, Quebec City, QC, Canada
- Department of Rehabilitation, Faculty of Medicine, Laval University, Quebec City, QC, Canada
| | - Audrey Desjardins
- Center for Interdisciplinary Research in Rehabilitation and Social Integration, Quebec City, QC, Canada
- Department of Rehabilitation, Faculty of Medicine, Laval University, Quebec City, QC, Canada
| | | | - Clémentine Brun
- Center for Interdisciplinary Research in Rehabilitation and Social Integration, Quebec City, QC, Canada
| | - Anne Marie Pinard
- Center for Interdisciplinary Research in Rehabilitation and Social Integration, Quebec City, QC, Canada
- Department of Anesthesiology and Intensive Care, Faculty of Medicine, Laval University, Quebec City, QC, Canada
| | - Martin Simoneau
- Center for Interdisciplinary Research in Rehabilitation and Social Integration, Quebec City, QC, Canada
- Department of Kinesiology, Faculty of Medicine, Laval University, Quebec City, QC, Canada
| | - Catherine Mercier
- Center for Interdisciplinary Research in Rehabilitation and Social Integration, Quebec City, QC, Canada
- Department of Rehabilitation, Faculty of Medicine, Laval University, Quebec City, QC, Canada
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26
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Othman R, Swain N, Tumilty S, Jayakaran P, Mani R. Pro-nociceptive pain modulation profile in patients with acute and chronic shoulder pain: a hypothesis-generating topical review. PHYSICAL THERAPY REVIEWS 2021. [DOI: 10.1080/10833196.2021.1973776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Affiliation(s)
- Rani Othman
- Centre for Health, Activity and Rehabilitation Research, School of Physiotherapy, University of Otago, Dunedin, New Zealand
| | - Nicola Swain
- Psychological Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand
- Pain@Otago Research Theme, University of Otago, Dunedin, New Zealand
| | - Steve Tumilty
- Centre for Health, Activity and Rehabilitation Research, School of Physiotherapy, University of Otago, Dunedin, New Zealand
| | - Prasath Jayakaran
- Centre for Health, Activity and Rehabilitation Research, School of Physiotherapy, University of Otago, Dunedin, New Zealand
| | - Ramakrishnan Mani
- Centre for Health, Activity and Rehabilitation Research, School of Physiotherapy, University of Otago, Dunedin, New Zealand
- Pain@Otago Research Theme, University of Otago, Dunedin, New Zealand
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27
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Cordón B, Orduna-Hospital E, Viladés E, Garcia-Martin E, Garcia-Campayo J, Puebla-Guedea M, Polo V, Larrosa JM, Pablo LE, Vicente MJ, Satue M. Analysis of Retinal Layers in Fibromyalgia Patients with Premium Protocol in Optical Tomography Coherence and Quality of Life. Curr Eye Res 2021; 47:143-153. [PMID: 34213409 DOI: 10.1080/02713683.2021.1951301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
PURPOSE To evaluate the inner retinal layers in fibromyalgia (FM) patients compared to control subjects using posterior pole protocol (PPole) analysis in optical coherence tomography (OCT) and to correlate structural retinal changes with subjective quality of life. METHODS Seventy-four eyes of healthy subjects and 55 eyes of those with FM were analyzed. All subjects underwent retinal evaluation using the PPole protocol for Spectralis OCT (Heidelberg Engineering) to obtain measurements of the retinal nerve fiber layer (RNFL) and the ganglion cell layer (GCL) in the macular area. The EuroQol (EQ-5D) questionnaire and Fibromyalgia Impact Questionnaire (FIQ) were performed to analyze health-related quality of life. Additionally, the FM group was divided into three groups depending on the disease phenotype (atypical, depressive and biological). RESULTS : Patients with FM presented with a reduction of the RNFL thickness compared to controls in 17/64 cells of the PPole area, and a reduction of the GCL thickness in 47/64 cells. Depressive FM phenotype showed the greatest number of cells with significant reduction compared with the control group in both RNFL and GCL layers. A correlation between temporal-inferior cells of the GCL and the EuroQol 5D questionnaire results was observed. CONCLUSIONS Patients with FM present with a reduction of the inner retinal layers in the macular area. This degeneration correlates with disease severity/reduced quality of life in these patients. The PPole protocol for OCT is a non-invasive and fast tool that might help clinicians diagnose and monitor neurodegeneration in FM patients.
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Affiliation(s)
- B Cordón
- Miguel Servet Ophthalmology Research and Innovative Group (GIMSO). Aragon Institute for Health Research (IIS Aragón). University of Zaragoza. Zaragoza (Spain).,Ophthalmology Department, Miguel Servet University Hospital. Zaragoza (Spain)
| | - E Orduna-Hospital
- Miguel Servet Ophthalmology Research and Innovative Group (GIMSO). Aragon Institute for Health Research (IIS Aragón). University of Zaragoza. Zaragoza (Spain).,Ophthalmology Department, Miguel Servet University Hospital. Zaragoza (Spain)
| | - E Viladés
- Miguel Servet Ophthalmology Research and Innovative Group (GIMSO). Aragon Institute for Health Research (IIS Aragón). University of Zaragoza. Zaragoza (Spain).,Ophthalmology Department, Miguel Servet University Hospital. Zaragoza (Spain)
| | - E Garcia-Martin
- Miguel Servet Ophthalmology Research and Innovative Group (GIMSO). Aragon Institute for Health Research (IIS Aragón). University of Zaragoza. Zaragoza (Spain).,Ophthalmology Department, Miguel Servet University Hospital. Zaragoza (Spain)
| | - J Garcia-Campayo
- Ophthalmology Department, Miguel Servet University Hospital. Zaragoza (Spain).,Psychiatry Department, Miguel Servet University Hospital, Zaragoza, Spain
| | - M Puebla-Guedea
- Aragon Institute for Health Research (IIS Aragón). University of Zaragoza. Zaragoza (Spain)
| | - V Polo
- Miguel Servet Ophthalmology Research and Innovative Group (GIMSO). Aragon Institute for Health Research (IIS Aragón). University of Zaragoza. Zaragoza (Spain).,Ophthalmology Department, Miguel Servet University Hospital. Zaragoza (Spain)
| | - J M Larrosa
- Miguel Servet Ophthalmology Research and Innovative Group (GIMSO). Aragon Institute for Health Research (IIS Aragón). University of Zaragoza. Zaragoza (Spain).,Ophthalmology Department, Miguel Servet University Hospital. Zaragoza (Spain)
| | - L E Pablo
- Miguel Servet Ophthalmology Research and Innovative Group (GIMSO). Aragon Institute for Health Research (IIS Aragón). University of Zaragoza. Zaragoza (Spain).,Ophthalmology Department, Miguel Servet University Hospital. Zaragoza (Spain)
| | - M J Vicente
- Miguel Servet Ophthalmology Research and Innovative Group (GIMSO). Aragon Institute for Health Research (IIS Aragón). University of Zaragoza. Zaragoza (Spain).,Ophthalmology Department, Miguel Servet University Hospital. Zaragoza (Spain)
| | - M Satue
- Miguel Servet Ophthalmology Research and Innovative Group (GIMSO). Aragon Institute for Health Research (IIS Aragón). University of Zaragoza. Zaragoza (Spain).,Ophthalmology Department, Miguel Servet University Hospital. Zaragoza (Spain)
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28
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Bunk S, Zuidema S, Koch K, Lautenbacher S, De Deyn PP, Kunz M. Pain processing in older adults with dementia-related cognitive impairment is associated with frontal neurodegeneration. Neurobiol Aging 2021; 106:139-152. [PMID: 34274699 DOI: 10.1016/j.neurobiolaging.2021.06.009] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 05/23/2021] [Accepted: 06/12/2021] [Indexed: 12/14/2022]
Abstract
Experimental pain research has shown that pain processing seems to be heightened in dementia. It is unclear which neuropathological changes underlie these alterations. This study examined whether differences in pressure pain sensitivity and endogenous pain inhibition (conditioned pain modulation (CPM)) between individuals with a dementia-related cognitive impairment (N=23) and healthy controls (N=35) are linked to dementia-related neurodegeneration. Pain was assessed via self-report ratings and by analyzing the facial expression of pain using the Facial Action Coding System. We found that cognitively impaired individuals show decreased CPM inhibition as assessed by facial responses compared to healthy controls, which was mediated by decreased gray matter volume in the medial orbitofrontal and anterior cingulate cortex in the patient group. This study confirms previous findings of intensified pain processing in dementia when pain is assessed using non-verbal responses. Our findings suggest that a loss of pain inhibitory functioning caused by structural changes in prefrontal areas might be one of the underlying mechanisms responsible for amplified pain responses in individuals with a dementia-related cognitive impairment.
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Affiliation(s)
- Steffie Bunk
- Department of General Practice and Elderly Care Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
| | - Sytse Zuidema
- Department of General Practice and Elderly Care Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Kathrin Koch
- Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; Graduate School of Systemic Neurosciences, Ludwig-Maximilians-Universität München, Martinsried, Germany
| | | | - Peter P De Deyn
- Alzheimer Center Groningen, Department Neurology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Miriam Kunz
- Department of General Practice and Elderly Care Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Department of Medical Psychology and Sociology, University of Augsburg, Augsburg, Germany
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29
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Consideration of Fibromyalgia in the Assessment and Treatment of SLE. CURRENT TREATMENT OPTIONS IN RHEUMATOLOGY 2021. [DOI: 10.1007/s40674-021-00181-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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30
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Leone C, Galosi S, Mollica C, Fortunato M, Possidente C, Milone V, Misuraca S, Berillo L, Truini A, Cruccu G, Ferrara M, Terrinoni A. Dissecting pain processing in adolescents with Non-Suicidal Self Injury: Could suicide risk lurk among the electrodes? Eur J Pain 2021; 25:1815-1828. [PMID: 33982830 PMCID: PMC8453562 DOI: 10.1002/ejp.1793] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Revised: 02/01/2021] [Accepted: 05/02/2021] [Indexed: 12/13/2022]
Abstract
Background Although non‐suicidal self‐injury (NSSI) disorder is highly prevalent in adolescents, its relationship with pain system function and suicidality is still controversial. The present study was designed to assess the function of the nociceptive afferent pathways and the endogenous pain modulation in adolescent patients with NSSI and to longitudinally register any suicide attempt, describe its frequency and find a possible association between suicide, neurophysiological measures and psychological measures. Methods We enrolled 30 adolescents suffering from NSSI and 20 age‐ and gender‐matched healthy controls. Patients underwent a comprehensive psychological evaluation. Each participant underwent thermal pain thresholds of the quantitative sensory testing, laser‐evoked potential recording to study the ascending nociceptive pathway and the conditioned pain modulation testing to test the endogenous pain modulation. Results We found that patients with NSSI had a reduced amplitude of the N2 component of laser‐evoked potentials and an abnormal conditioned pain modulation. The amplitude of the N2 was associated with suicidal risk. Conclusions The deficit of the endogenous pain modulation likely depends on a saturation due to continuous pain solicitation. The strong association of a reduced amplitude of the N2 component with suicide suggests that it may serve as a possible biomarker in self‐harming adolescents. Significance The present study identifies the N2 component of laser‐evoked potentials as a possible neurophysiological biomarker of suicidal risk in patients with non‐suicidal self‐injury, therefore, raising the possibility for a non‐invasive test to identify subjects at higher risk of suicide among self‐harming patients.
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Affiliation(s)
- Caterina Leone
- Department of Human Neuroscience, Sapienza University, Rome, Italy
| | - Serena Galosi
- Department of Human Neuroscience, Sapienza University, Rome, Italy
| | - Cristina Mollica
- Department of Methods and Models for Economics, Territory and Finance, Sapienza University, Rome, Italy
| | - Mattia Fortunato
- Department of Human Neuroscience, Sapienza University, Rome, Italy
| | | | - Valeria Milone
- Department of Human Neuroscience, Sapienza University, Rome, Italy
| | - Sofia Misuraca
- Department of Human Neuroscience, Sapienza University, Rome, Italy
| | - Luana Berillo
- Department of Human Neuroscience, Sapienza University, Rome, Italy
| | - Andrea Truini
- Department of Human Neuroscience, Sapienza University, Rome, Italy
| | - Giorgio Cruccu
- Department of Human Neuroscience, Sapienza University, Rome, Italy
| | - Mauro Ferrara
- Department of Human Neuroscience, Sapienza University, Rome, Italy
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31
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Amer-Cuenca JJ, Pecos-Martín D, Martínez-Merinero P, Lluch Girbés E, Nijs J, Meeus M, Ferrer Peña R, Fernández-Carnero J. How Much Is Needed? Comparison of the Effectiveness of Different Pain Education Dosages in Patients with Fibromyalgia. PAIN MEDICINE 2021; 21:782-793. [PMID: 31216027 DOI: 10.1093/pm/pnz069] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
OBJECTIVE To assess the effect of different dosages of pain neuroscience education (PNE) programs on central nociceptive processing in patients with fibromyalgia. Second, to compare the effects of different dosages of PNE programs on numerical pain rating scale (NPRS), disability, and psychological variables. DESIGN Single-blind randomized controlled trial. SETTING Three fibromyalgia centers in Spain (Valencia, Alcorcón, Alcalá de Henares). SUBJECTS Seventy-seven patients with fibromyalgia. METHODS Participants were randomized to four groups of PNE: 1) high-dose PNE (N = 20), 2) low-concentrated dose PNE (N = 20), 3) diluted low-dose PNE (N = 20), and (4) control treatment (N = 17), conducted in two 30-50-minute sessions in groups of four to six participants. Conditioned pain modulation (CPM), temporal summation (TS), and pressure pain thresholds (PPTs) were assessed at baseline and at three-month follow-up. Secondary outcome measures were the Fibromyalgia Impact Questionnaire, Pain Catastrophizing Scale, and Pain Anxiety Symptoms Scale. RESULTS There were significant between-group differences for NPRS in favor of the groups receiving high-dose PNE, with a large effect size at three-month follow-up (P < 0.01, η2p = 0.170), but there were no significant differences between groups for the remaining variables (P > 0.05). All groups improved for central nociceptive processing, psychological variables, disability, and pain intensity (NPRS). CONCLUSIONS In patients with fibromyalgia, higher dosages of PNE produced a larger improvement in pain severity at three-month follow-up than other dosages of PNE and biomedical education. However, PNE was not superior to biomedical education in the central nociceptive processing, disability, or psychological variables in patients with fibromyalgia.
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Affiliation(s)
- Juan J Amer-Cuenca
- Department of Physiotherapy, Universidad Cardenal Herrera-CEU, CEU Universities, Valencia, Spain
| | - Daniel Pecos-Martín
- Department of Nursing and Physiotheraphy, Universidad de Alcalá, Alcalá de Henares, Spain
| | | | - Enrique Lluch Girbés
- Department of Physiotherapy, Universitat de València, Valencia, Spain.,Pain in Motion International Research Group, www.paininmotion.be
| | - Jo Nijs
- Pain in Motion International Research Group, www.paininmotion.be.,Department of Physiotherapy, Physiology and Anatomy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium.,Department of Physical Medicine and Physiotherapy, University Hospital Brussels, Brussels, Belgium
| | - Mira Meeus
- Pain in Motion International Research Group, www.paininmotion.be.,Department Movant, Faculty of Medicine and Health Sciences, University of Antwerp, Belgium.,Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Sciences, Ghent University, Belgium
| | - Raúl Ferrer Peña
- Physical Therapy Department and Motion in Brains Research Group, Instituto de Neurociencias y Ciencias del Movimiento (INCIMOV), Centro Superior de Estudios Universitarios La Salle, Universidad Auta de Madrid, Spain.,Centro de Salud Entrevías. Gerencia de Atenciñn Primaria. Servicio Madrile𭟤e Salud, Madrid, Spain
| | - Josué Fernández-Carnero
- Physical Therapy Department and Motion in Brains Research Group, Instituto de Neurociencias y Ciencias del Movimiento (INCIMOV), Centro Superior de Estudios Universitarios La Salle, Universidad Auta de Madrid, Spain.,Department of Physiotherapy, Occupational Therapy, Rehabilitation and Physical Medicine, Rey Juan Carlos University, Madrid, Spain.,Foundation for Biomedical Research, La Paz University Hospital, IDIPAZ, Madrid, Spain
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32
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A Systematic Review Into the Influence of Temperature on Fibromyalgia Pain: Meteorological Studies and Quantitative Sensory Testing. THE JOURNAL OF PAIN 2021; 22:473-486. [PMID: 33421589 DOI: 10.1016/j.jpain.2020.12.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 10/03/2020] [Accepted: 12/15/2020] [Indexed: 01/01/2023]
Abstract
Fibromyalgia syndrome (FMS) is a chronic widespread pain condition of unknown aetiology. The role of temperature in FMS pain has not been reviewed systematically. The goal of this study was to review the influences of temperature on pain in FMS, from meteorological and quantitative sensory testing (QST) studies. The review was registered with Prospero: ID-CRD42020167687, and followed PRISMA guidance. Databases interrogated were: MEDLINE (via OVID), EMBASE, PubMed, Web of Science, ScienceDirect, CINAHL, and ProQuest (Feb'20). Exclusion criteria were: age <18, animal studies, non-English, and noncontrolled articles. Thirteen studies pertaining to ambient temperature and FMS pain were identified; 9 of these found no uniform relationship. Thirty-five QST studies were identified, 17 of which assessed cold pain thresholds (CPTs). All studies showed numerically reduced CPTs in patients, ranging from 10.9°C to 26.3°C versus 5.9°C to 13.5°C in controls; this was statistically significant in 14/17. Other thermal thresholds were often abnormal. We conclude that the literature provides consistent evidence for an abnormal sensitization of FMS patients' temperature-sensation systems. Additional work is required to elucidate the factors that determine why a subgroup of patients perceive low ambient temperatures as painful, and to characterize that group. PERSPECTIVE: Patients often report increased pain with changes in ambient temperature; even disabling, extreme temperature sensitivity in winter. Understanding this phenomenon may help clinicians provide reassurance and advice to patients and may guide research into the everyday impact of such hypersensitivity, whilst directing future work into the pathophysiology of FMS.
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Ramaswamy S, Wodehouse T. Conditioned pain modulation-A comprehensive review. Neurophysiol Clin 2020; 51:197-208. [PMID: 33334645 DOI: 10.1016/j.neucli.2020.11.002] [Citation(s) in RCA: 96] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 11/25/2020] [Accepted: 11/28/2020] [Indexed: 01/05/2023] Open
Abstract
Conditioned pain modulation (CPM) is a centrally processed measure of the net effect of the descending pain pathway. This comprises both the facilitatory as well as the inhibitory effect. In the past, CPM or similar effects have been previously described using different terminologies such as diffuse noxious inhibitory control (DNIC), heterotopic noxious conditioning stimulation (HNCS) or endogenous analgesia (EA). A variety of patient-related factors such as age, gender, hormones, race, genetic and psychological factors have been thought to influence the CPM paradigms. CPM paradigms have also been associated with a wide range of methodological variables including the mode of application of the 'test' as well as the 'conditioning' stimuli. Despite all these variabilities, CPM seems to reliably lend itself to the pain modulation profile concept and could in future become one of the phenotypic biomarkers for pain and also a guide for mechanism-based treatment in chronic pain. Future research should focus on establishing consistent methodologies for measuring CPM and thereby enhancing the robustness of this emerging biomarker for pain.
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Affiliation(s)
- Shankar Ramaswamy
- 1St Bartholomew's Hospital, Bart's Health NHS Trust, London, EC1A 4AS, UK.
| | - Theresa Wodehouse
- 1St Bartholomew's Hospital, Bart's Health NHS Trust, London, EC1A 4AS, UK
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Irvine KA, Sahbaie P, Ferguson AR, Clark JD. Loss of diffuse noxious inhibitory control after traumatic brain injury in rats: A chronic issue. Exp Neurol 2020; 333:113428. [PMID: 32745472 PMCID: PMC11793995 DOI: 10.1016/j.expneurol.2020.113428] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 07/23/2020] [Accepted: 07/25/2020] [Indexed: 02/07/2023]
Abstract
Chronic pain is one of the most challenging and debilitating symptoms to manage after traumatic brain injury (TBI), yet the underlying mechanisms remain elusive. The disruption of normal endogenous pain control mechanisms has been linked to several forms of chronic pain and may play a role in pain after TBI. We hypothesized therefore that dysfunctional descending noradrenergic and serotonergic pain control circuits may contribute to the loss of diffuse noxious inhibitory control (DNIC), a critical endogenous pain control mechanism, weeks to months after TBI. For these studies, the rat lateral fluid percussion model of mild TBI was used along with a DNIC paradigm involving a capsaicin-conditioning stimulus. We observed sustained failure of the DNIC response up to 180-days post injury. We confirmed, that descending α2 adrenoceptor-mediated noradrenergic signaling was critical for endogenous pain inhibition in uninjured rats. However, augmenting descending noradrenergic signaling using reboxetine, a selective noradrenaline reuptake inhibitor, failed to restore DNIC after TBI. Furthermore, blocking serotonin-mediated descending signaling using selective spinal serotonergic fiber depletion with 5, 7-dihydroxytryptamine was also unsuccessful at restoring endogenous pain modulation after TBI. Unexpectedly, increasing descending serotonergic signaling using the selective serotonin reuptake inhibitor escitalopram and the serotonin-norepinephrine reuptake inhibitor duloxetine restored the DNIC response in TBI rats at both 49- and 180- days post injury. Consistent with these observations, spinal serotonergic fiber depletion with 5, 7-dihydroxytryptamine eliminated the effects of escitalopram. Intact α2 adrenoceptor signaling, however, was not required for the serotonin-mediated restoration of DNIC after TBI. These results suggest that TBI causes maladaptation of descending nociceptive signaling mechanisms and changes in the function of both adrenergic and serotonergic circuits. Such changes could predispose those with TBI to chronic pain.
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Affiliation(s)
- Karen-Amanda Irvine
- Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, School of Medicine, Stanford, CA 94305, USA; Anesthesiology Service, Veterans Affairs Palo Alto Health Care System, 3801 Miranda Ave (E4-220), Palo Alto, CA 94304, USA.
| | - Peyman Sahbaie
- Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, School of Medicine, Stanford, CA 94305, USA; Anesthesiology Service, Veterans Affairs Palo Alto Health Care System, 3801 Miranda Ave (E4-220), Palo Alto, CA 94304, USA
| | - Adam R Ferguson
- University of California San Francisco, Brain and Spinal Injury Center, Department Neurosurgery, 1001 Potrero Ave, San Francisco, CA 94110, USA
| | - J David Clark
- Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, School of Medicine, Stanford, CA 94305, USA; Anesthesiology Service, Veterans Affairs Palo Alto Health Care System, 3801 Miranda Ave (E4-220), Palo Alto, CA 94304, USA
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Casteluci CEVF, Oltramari PVP, Conti PCR, Bonjardim LR, de Almeida-Pedrin RR, Fernandes TMF, de Almeida MR, de Castro Ferreira Conti AC. Evaluation of pain intensity in patients treated with aligners and conventional fixed appliances: Randomized clinical trial. Orthod Craniofac Res 2020; 24:268-276. [PMID: 33058419 DOI: 10.1111/ocr.12431] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 09/23/2020] [Accepted: 10/07/2020] [Indexed: 01/01/2023]
Abstract
OBJECTIVE This randomized clinical trial aimed to compare the pain intensity in patients treated with orthodontic aligners and conventional fixed appliances. SETTING AND SAMPLE POPULATION This study was a randomized clinical trial. The sample comprised 39 patients randomly allocated into 2 groups: OA (orthodontic aligners, n = 20) and FA (Fixed Appliance, n = 19). MATERIAL AND METHODS The pain intensity was measured by the visual analogue scale (VAS) in the following periods: T0 (baseline), T1 (seven days after appliance placement) and seven days after each return on the first (T2), third (T3) and sixth (T4) months. The following variables were also investigated in the baseline: conditioned pain modulation, anxiety levels, hypervigilance and catastrophizing. The VAS measurements between groups were compared by the Mann-Whitney test. Comparisons between periods within each group were performed by the Friedman test. Data regarding catastrophizing and hypervigilance were compared by the t test. All tests were applied at a significance level of 5%, with 95% confidence interval. RESULTS Both groups presented similar levels of anxiety, hypervigilance, catastrophizing and conditioned pain modulation. Both groups did not differ concerning the pain intensity in all periods. The intragroup evaluation revealed statistical differences between days in the FA group at all moments evaluated, for the OA group, similar findings between days were found for the T1 evaluation; however, at the 6-month period (T4), the pain levels varied over these days without statistical difference. Higher levels of pain were observed in the first seven days after appliance placement. CONCLUSION The pain intensity, usually mild, was not influenced by the appliance design, although different patterns of reported pain seem to occur between groups.
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Affiliation(s)
| | | | - Paulo César Rodrigues Conti
- Department of Prosthodontics, Bauru School of Dentistry, Bauru Orofacial Pain Group, University of São Paulo, São Paulo, Brazil
| | - Leonardo Rigoldi Bonjardim
- Section of Head and Face Physiology, Department of Biological Sciences, Bauru School of Dentistry, Bauru Orofacial Pain Group, University of São Paulo, São Paulo, Brazil
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Berger AA, Keefe J, Winnick A, Gilbert E, Eskander JP, Yazdi C, Kaye AD, Viswanath O, Urits I. Cannabis and cannabidiol (CBD) for the treatment of fibromyalgia. Best Pract Res Clin Anaesthesiol 2020; 34:617-631. [PMID: 33004171 DOI: 10.1016/j.bpa.2020.08.010] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 08/12/2020] [Indexed: 12/19/2022]
Abstract
Fibromyalgia is a complex disease process that is as prevalent as it is poorly understood. Research into the pathophysiology is ongoing, and findings will likely assist in identifying new therapeutic options to augment those in existence today that are still insufficient for the care of a large population of patients. Recent evidence describes the use of cannabinoids in the treatment of fibromyalgia. This study provides a systematic, thorough review of the evidence alongside a review of the seminal data regarding the pathophysiology, diagnosis, and current treatment options. Fibromyalgia is characterized by widespread chronic pain, fatigue, and depressive episodes without an organic diagnosis, which may be prevalent in up to 10% of the population and carries a significant cost in healthcare utilization, morbidity, a reduced quality of life, and productivity. It is frequently associated with psychiatric comorbidities. The diagnosis is clinical and usually prolonged, and diagnostic criteria continue to evolve. Some therapies have been previously described, including neuropathic medications, milnacipran, and antidepressants. Despite some level of efficacy, only physical exercise has strong evidence to support it. Cannabis has been used historically to treat different pain conditions since ancient times. Recent advances allowed for the isolation of the active substances in cannabis and the production of cannabinoid products that are nearly devoid of psychoactive influence and provide pain relief and alleviation of other symptoms. Many of these, as well as cannabis itself, are approved for use in chronic pain conditions. Evidence supporting cannabis in chronic pain conditions is plentiful; however, in fibromyalgia, they are mostly limited. Only a handful of randomized trials exists, and their objectivity has been questioned. However, many retrospective trials and patient surveys suggest the significant alleviation of pain, improvement in sleep, and abatement of associated symptoms. Evidence supporting the use of cannabis in chronic pain and specifically in fibromyalgia is being gathered as the use of cannabis increases with current global trends. While the current evidence is still limited, emerging data do suggest a positive effect of cannabis in fibromyalgia. Cannabis use is not without risks, including psychiatric, cognitive, and developmental as well as the risks of addiction. As such, clinical judgment is warranted to weigh these risks and prescribe to patients who are more likely to benefit from this treatment. Further research is required to define appropriate patient selection and treatment regimens.
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Affiliation(s)
- Amnon A Berger
- Beth Israel Deaconess Medical Center, Department of Anesthesiology, Critical Care, and Pain Medicine, Harvard Medical School, Boston, MA, USA.
| | - Joseph Keefe
- Ben-Gurion University of the Negev Medical School for International Health, Beer-Sheva, Israel
| | - Ariel Winnick
- Ben-Gurion University of the Negev Medical School for International Health, Beer-Sheva, Israel
| | - Elasaf Gilbert
- Ben-Gurion University of the Negev Medical School for International Health, Beer-Sheva, Israel
| | - Jonathan P Eskander
- Portsmouth Anesthesia Associates, Anesthesiology and Pain Medicine, Portsmouth, VA, USA
| | - Cyrus Yazdi
- Beth Israel Deaconess Medical Center, Department of Anesthesiology, Critical Care, and Pain Medicine, Harvard Medical School, Boston, MA, USA
| | - Alan D Kaye
- Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA, USA
| | - Omar Viswanath
- Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA, USA; University of Arizona College of Medicine - Phoenix, Department of Anesthesiology, Phoenix, AZ, USA; Creighton University School of Medicine, Department of Anesthesiology, Omaha, NE, USA; Valley Pain Consultants - Envision Physician Services, Phoenix, AZ, USA
| | - Ivan Urits
- Beth Israel Deaconess Medical Center, Department of Anesthesiology, Critical Care, and Pain Medicine, Harvard Medical School, Boston, MA, USA
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Bunk S, Emch M, Koch K, Lautenbacher S, Zuidema S, Kunz M. Pain Processing in Older Adults and Its Association with Prefrontal Characteristics. Brain Sci 2020; 10:brainsci10080477. [PMID: 32722197 PMCID: PMC7465457 DOI: 10.3390/brainsci10080477] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 07/17/2020] [Accepted: 07/22/2020] [Indexed: 02/02/2023] Open
Abstract
Aging is known to affect nociceptive processing, e.g., the ability to inhibit pain. This study aims to investigate whether pain responses in older individuals are associated with prefrontal characteristics, namely (i) executive functioning performance and (ii) structural brain variations in the prefrontal cortex. Heat and pressure stimuli were applied to assess pressure pain sensitivity and endogenous pain inhibition in 46 healthy older individuals. Executive functioning performance was assessed in three domains (i.e., cognitive inhibition, shifting, and updating) and structural brain variations were assessed in both gray and white matter. Overall pain responses were significantly associated with the executive functioning domains cognitive inhibition and shifting. However, no specific type of pain response showed an especially strong association. Endogenous pain inhibition specifically showed a significant association with gray matter volume in the prefrontal cortex and with variations in white matter structure of tracts connecting the prefrontal cortex with the periaqueductal gray. Hierarchical regression analyses showed that these variations in the prefrontal cortex can explain variance in pain inhibition beyond what can be explained by executive functioning. This might indicate that known deficits in pain inhibition in older individuals are associated with structural variations in prefrontal areas.
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Affiliation(s)
- Steffie Bunk
- Department of General Practice and Elderly Care Medicine, University Medical Center Groningen, University of Groningen, 9713GZ Groningen, The Netherlands; (S.Z.); (M.K.)
- Correspondence: ; Tel.: +31-503616686
| | - Mónica Emch
- Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany; (M.E.); (K.K.)
- Graduate School of Systemic Neurosciences, Ludwig-Maximilians-Universität München, 82152 Martinsried, Germany
| | - Kathrin Koch
- Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany; (M.E.); (K.K.)
- Graduate School of Systemic Neurosciences, Ludwig-Maximilians-Universität München, 82152 Martinsried, Germany
| | | | - Sytse Zuidema
- Department of General Practice and Elderly Care Medicine, University Medical Center Groningen, University of Groningen, 9713GZ Groningen, The Netherlands; (S.Z.); (M.K.)
| | - Miriam Kunz
- Department of General Practice and Elderly Care Medicine, University Medical Center Groningen, University of Groningen, 9713GZ Groningen, The Netherlands; (S.Z.); (M.K.)
- Department of Medical Psychology and Sociology, University of Augsburg, 86159 Augsburg, Germany
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da Rocha AP, Mizzaci CC, Nunes Pinto ACP, da Silva Vieira AG, Civile V, Trevisani VFM. Tramadol for management of fibromyalgia pain and symptoms: Systematic review. Int J Clin Pract 2020; 74:e13455. [PMID: 31799728 DOI: 10.1111/ijcp.13455] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Revised: 11/26/2019] [Accepted: 11/27/2019] [Indexed: 11/28/2022] Open
Abstract
BACKGROUND Fibromyalgia is a heterogeneous condition that appears to be associated with physiological and biochemical disturbances of pain modulation, and that consequently affects numerous other facets of life. Tramadol is currently being explored as an option to manage fibromyalgia pain and other symptoms because of its inhibitory activity of reuptake of neurotransmitters, but its safety and efficacy have not yet been established in these patients. OBJECTIVE To evaluate the effectiveness and safety of tramadol on the management of symptoms of the syndrome. METHODS We searched CENTRAL, MEDLINE, EMBASE, LILACS, Opengrey, ClinicalTrials.gov and WHO-ICTRP for randomised controlled trials analysing the association between tramadol used for fibromyalgia either single-agent or in combination with other drugs. Two reviewers independently extracted data and assessed risk of bias using the Cochrane risk-of-bias tool for all included studies. Quality of the evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS Four RCTs comprising 459 patients were included. Tramadol-either as a single-agent or in combination with an antidepressant or analgesic-had a positive effect on pain. Tramadol combined with analgesic showed improved quality of life over placebo as measured by the Fibromyalgia Impact Questionnaire at 91 days. However, this difference did not hold for tramadol as a single agent against placebo. The evidence in these articles was rated "low" using the GRADE approach. No serious adverse events were reported. No improvement in depression and quality of sleep were observed. CONCLUSIONS This systematic review found a dearth of clinical trials on tramadol in patients with fibromyalgia. Although the combination of monoamine and opioid mechanism of tramadol has shown positive effects for fibromyalgia, the available evidence is not sufficient to support or refute the use of tramadol in clinical practice for pain or symptom management. Protocol registration number in the PROSPERO database: CRD42017062139.
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Affiliation(s)
- Aline Pereira da Rocha
- Discipline of Evidence-Based Health, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil
- Cochrane Brazil, São Paulo, Brazil
| | - Carolina Christianini Mizzaci
- Discipline of Evidence-Based Health, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil
- Cochrane Brazil, São Paulo, Brazil
| | - Ana Carolina Pereira Nunes Pinto
- Discipline of Evidence-Based Health, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil
- Cochrane Brazil, São Paulo, Brazil
- Department of Biological and Health Sciences, Federal University of Para, Belém, Pará, Brazil
- University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Alexia Gabriela da Silva Vieira
- Discipline of Evidence-Based Health, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil
- Cochrane Brazil, São Paulo, Brazil
| | - Vinicius Civile
- Discipline of Evidence-Based Health, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil
- Cochrane Brazil, São Paulo, Brazil
| | - Virgínia Fernandes Moça Trevisani
- Discipline of Evidence-Based Health, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil
- Cochrane Brazil, São Paulo, Brazil
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Hollins M, Bryen CP, Taylor D. Effects of chronic pain history on perceptual and cognitive inhibition. Exp Brain Res 2020; 238:321-332. [PMID: 31907554 DOI: 10.1007/s00221-019-05715-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Accepted: 12/18/2019] [Indexed: 01/01/2023]
Abstract
Measures of sensory and cognitive inhibition were obtained from university students with and without a history of chronic pain. The form of sensory inhibition measured was diffuse noxious inhibitory controls (DNIC), the capacity of a painful stimulus to reduce the subjective intensity of a second stimulus delivered to a remote body site. To measure cognitive inhibition, the Stroop effect was used. Participants with a history of chronic pain showed less DNIC (i.e., less sensory inhibition) than the healthy controls, but had a smaller Stroop effect (indicating greater cognitive inhibition). The fact that chronic pain history is associated with opposite changes in these two measures casts doubt on the view that the two inhibitory processes are related. Scores on each experimental measure were equivalent in pain-history subjects with ongoing chronic pain and those whose chronic pain had resolved. This equivalence suggests that chronic pain in childhood or adolescence may have lingering effects on sensory and cognitive inhibition.
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Affiliation(s)
- Mark Hollins
- Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
| | - Chloe P Bryen
- Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
| | - Dillon Taylor
- Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
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Gozani SN. Remote Analgesic Effects Of Conventional Transcutaneous Electrical Nerve Stimulation: A Scientific And Clinical Review With A Focus On Chronic Pain. J Pain Res 2019; 12:3185-3201. [PMID: 31819603 PMCID: PMC6885653 DOI: 10.2147/jpr.s226600] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Accepted: 11/02/2019] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Transcutaneous electrical nerve stimulation (TENS) is a safe, noninvasive treatment for chronic pain that can be self-administered. Conventional TENS involves stimulation of peripheral sensory nerves at a strong, non-painful level. Following the original gate-control theory of pain, stimulation is typically near the target pain. As another option, remote stimulation may also be effective and offers potential advantages. OBJECTIVE This narrative review examines mechanisms underlying the remote analgesic effects of conventional TENS and appraises the clinical evidence. METHODS A literature search for English-language articles was performed on PubMed. Keywords included terms related to the location of TENS . Citations from primary references and textbooks were examined for additional articles. RESULTS Over 30 studies reported remote analgesic effects of conventional TENS. The evidence included studies using animal models of pain, experimental pain in humans, and clinical studies in subjects with chronic pain. Three types of remote analgesia were identified: at the contralateral homologous site, at sites distant from stimulation but innervated by overlapping spinal segments, and at unrelated extrasegmental sites. CONCLUSION There is scientific and clinical evidence that conventional TENS has remote analgesic effects. This may occur through modulation of pain processing at the level of the dorsal horn, in brainstem centers mediating descending inhibition, and within the pain matrix. A broadening of perspectives on how conventional TENS produces analgesia may encourage researchers, clinicians, and medical-device manufacturers to develop novel ways of using this safe, cost-effective neuromodulation technique for chronic pain.
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Ellingson LD, Stegner AJ, Schwabacher IJ, Lindheimer JB, Cook DB. Catastrophizing Interferes with Cognitive Modulation of Pain in Women with Fibromyalgia. PAIN MEDICINE 2019; 19:2408-2422. [PMID: 29474665 DOI: 10.1093/pm/pny008] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Background Pain modulation is a critical function of the nociceptive system that includes the ability to engage descending pain control systems to maintain a functional balance between facilitation and inhibition of incoming sensory stimuli. Dysfunctional pain modulation is associated with increased risk for chronic pain and is characteristic of fibromyalgia (FM). Catastrophizing is also common in FM. However, its influence on pain modulation is poorly understood. Objective To determine the role of catastrophizing on central nervous system processing during pain modulation in FM via examining brain responses and pain sensitivity during an attention-distraction paradigm. Methods Twenty FM patients and 18 healthy controls (CO) underwent functional magnetic resonance imaging while receiving pain stimuli, administered alone and during distracting cognitive tasks. Pain ratings were assessed after each stimulus. Catastrophizing was assessed with the Pain Catastrophizing Scale (PCS). Results The ability to modulate pain during distraction varied among FM patients and was associated with catastrophizing. This was demonstrated by significant positive relationships between PCS scores and pain ratings (P < 0.05) and brain responses in the dorsolateral prefrontal cortex (P < 0.01). Relationships between catastrophizing and pain modulation did not differ between FM and CO (P > 0.05). Conclusions FM patients with higher levels of catastrophizing were less able to distract themselves from pain, indicative of catastrophizing-related impairments in pain modulation. These results suggest that the tendency to catastrophize interacts with attention-resource allocation and may represent a mechanism of chronic pain exacerbation and/or maintenance. Reducing catastrophizing may improve FM symptoms via improving central nervous system regulation of pain.
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Affiliation(s)
- Laura D Ellingson
- William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin.,Department of Kinesiology, University of Wisconsin-Madison, Madison, Wisconsin.,Department of Kinesiology, Iowa State University, Ames, Iowa, USA
| | - Aaron J Stegner
- William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin.,Department of Kinesiology, University of Wisconsin-Madison, Madison, Wisconsin
| | - Isaac J Schwabacher
- William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin.,Department of Kinesiology, University of Wisconsin-Madison, Madison, Wisconsin
| | - Jacob B Lindheimer
- William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin.,Department of Kinesiology, University of Wisconsin-Madison, Madison, Wisconsin
| | - Dane B Cook
- William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin.,Department of Kinesiology, University of Wisconsin-Madison, Madison, Wisconsin
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Khanna R, Patwardhan A, Yang X, Li W, Cai S, Ji Y, Chew LA, Dorame A, Bellampalli SS, Schmoll RW, Gordon J, Moutal A, Vanderah TW, Porreca F, Ibrahim MM. Development and Characterization of An Injury-free Model of Functional Pain in Rats by Exposure to Red Light. THE JOURNAL OF PAIN 2019; 20:1293-1306. [PMID: 31054915 DOI: 10.1016/j.jpain.2019.04.008] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Revised: 02/23/2019] [Accepted: 04/15/2019] [Indexed: 12/19/2022]
Abstract
We report the development and characterization of a novel, injury-free rat model in which nociceptive sensitization after red light is observed in multiple body areas reminiscent of widespread pain in functional pain syndromes. Rats were exposed to red light-emitting diodes (RLED) (LEDs, 660 nm) at an intensity of 50 Lux for 8 hours daily for 5 days resulting in time- and dose-dependent thermal hyperalgesia and mechanical allodynia in both male and female rats. Females showed an earlier onset of mechanical allodynia than males. The pronociceptive effects of RLED were mediated through the visual system. RLED-induced thermal hyperalgesia and mechanical allodynia were reversed with medications commonly used for widespread pain, including gabapentin, tricyclic antidepressants, serotonin/norepinephrine reuptake inhibitors, and nonsteroidal anti-inflammatory drugs. Acetaminophen failed to reverse the RLED induced hypersensitivity. The hyperalgesic effects of RLED were blocked when bicuculline, a gamma-aminobutyric acid-A receptor antagonist, was administered into the rostral ventromedial medulla, suggesting a role for increased descending facilitation in the pain pathway. Key experiments were subjected to a replication study with randomization, investigator blinding, inclusion of all data, and high levels of statistical rigor. RLED-induced thermal hyperalgesia and mechanical allodynia without injury offers a novel injury-free rodent model useful for the study of functional pain syndromes with widespread pain. RLED exposure also emphasizes the different biological effects of different colors of light exposure. PERSPECTIVE: This study demonstrates the effect of light exposure on nociceptive thresholds. These biological effects of red LED add evidence to the emerging understanding of the biological effects of light of different colors in animals and humans. Understanding the underlying biology of red light-induced widespread pain may offer insights into functional pain states.
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Affiliation(s)
- Rajesh Khanna
- Department of Anesthesiology, University of Arizona, Tucson, Arizona; Department of Pharmacology, University of Arizona, Tucson, Arizona; Department of Graduate Interdisciplinary Program in Neuroscience College of Medicine, University of Arizona, Tucson, Arizona
| | - Amol Patwardhan
- Department of Anesthesiology, University of Arizona, Tucson, Arizona; Department of Pharmacology, University of Arizona, Tucson, Arizona
| | - Xiaofang Yang
- Department of Pharmacology, University of Arizona, Tucson, Arizona
| | - Wennan Li
- Department of Pharmacology, University of Arizona, Tucson, Arizona
| | - Song Cai
- Department of Pharmacology, University of Arizona, Tucson, Arizona
| | - Yingshi Ji
- Department of Pharmacology, University of Arizona, Tucson, Arizona
| | - Lindsey A Chew
- Department of Pharmacology, University of Arizona, Tucson, Arizona
| | - Angie Dorame
- Department of Pharmacology, University of Arizona, Tucson, Arizona
| | | | - Ryan W Schmoll
- Department of Anesthesiology, University of Arizona, Tucson, Arizona
| | - Janalee Gordon
- Department of Anesthesiology, University of Arizona, Tucson, Arizona
| | - Aubin Moutal
- Department of Pharmacology, University of Arizona, Tucson, Arizona
| | - Todd W Vanderah
- Department of Pharmacology, University of Arizona, Tucson, Arizona
| | - Frank Porreca
- Department of Anesthesiology, University of Arizona, Tucson, Arizona; Department of Pharmacology, University of Arizona, Tucson, Arizona
| | - Mohab M Ibrahim
- Department of Anesthesiology, University of Arizona, Tucson, Arizona; Department of Pharmacology, University of Arizona, Tucson, Arizona.
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Altas EU, Askin A, Beşiroğlu L, Tosun A. Is high-frequency repetitive transcranial magnetic stimulation of the left primary motor cortex superior to the stimulation of the left dorsolateral prefrontal cortex in fibromyalgia syndrome? Somatosens Mot Res 2019; 36:56-62. [DOI: 10.1080/08990220.2019.1587400] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Affiliation(s)
- Elif Umay Altas
- Physical Medicine and Rehabilitation, Izmir Ataturk Egitim ve Arastirma Hastanesi, Katip Celebi University Ataturk Education and Research Hospital, Izmir, Turkey
| | - Ayhan Askin
- Physical Medicine and Rehabilitation, Izmir Katip Celebi Universitesi, Izmir, Turkey
| | | | - Aliye Tosun
- Physical Medicine and Rehabilitation, Izmir Katip Celebi Universitesi, Izmir, Turkey
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45
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Cutaneous silent periods – Part 2: Update on pathophysiology and clinical utility. Clin Neurophysiol 2019; 130:604-615. [DOI: 10.1016/j.clinph.2019.01.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Revised: 12/28/2018] [Accepted: 01/08/2019] [Indexed: 02/08/2023]
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46
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Brighina F, Curatolo M, Cosentino G, De Tommaso M, Battaglia G, Sarzi-Puttini PC, Guggino G, Fierro B. Brain Modulation by Electric Currents in Fibromyalgia: A Structured Review on Non-invasive Approach With Transcranial Electrical Stimulation. Front Hum Neurosci 2019; 13:40. [PMID: 30804771 PMCID: PMC6378756 DOI: 10.3389/fnhum.2019.00040] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Accepted: 01/24/2019] [Indexed: 01/13/2023] Open
Abstract
Fibromyalgia syndrome (FMS) is a complex disorder where widespread musculoskeletal pain is associated with many heterogenous symptoms ranging from affective disturbances to cognitive dysfunction and central fatigue. FMS is currently underdiagnosed and often very poorly responsive to pharmacological treatment. Pathophysiology of the disease remains still obscure even if in the last years fine structural and functional cerebral abnormalities have been identified, principally by neurophysiological and imaging studies delineating disfunctions in pain perception, processing and control systems. On such basis, recently, neurostimulation of brain areas involved in mechanism of pain processing and control (primary motor cortex: M1 and dorsolateral prefrontal cortex: DLPFC) has been explored by means of different approaches and particularly through non-invasive brain stimulation techniques (transcranial magnetic and electric stimulation: TMS and tES). Here we summarize studies on tES application in FMS. The great majority of reports, based on direct currents (transcranial direct currents stimulation: tDCS) and targeting M1, showed efficacy on pain measures and less on cognitive and affective symptoms, even if several aspects as maintenance of therapeutical effects and optimal stimulation parameters remain to be established. Differently, stimulation of DLPFC, explored in a few studies, was ineffective on pain and showed limited effects on cognitive and affective symptoms. Very recently new tES techniques as high-density tDCS (HD-tDCS), transcranial random noise stimulation (tRNS) and tDCS devices for home-based treatment have been explored in FMS with interesting even if very preliminary results opening interesting perspectives for more effective, well tolerated, cheap and easy therapeutic approaches.
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Affiliation(s)
- Filippo Brighina
- Dipartimento di Biomedicina, Neuroscienze e Diagnostica Avanzata (BIND), Università degli Studi di Palermo, Palermo, Italy
| | - Massimiliano Curatolo
- Dipartimento di Biomedicina, Neuroscienze e Diagnostica Avanzata (BIND), Università degli Studi di Palermo, Palermo, Italy
| | - Giuseppe Cosentino
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.,IRCCS Mondino Foundation, Pavia, Italy
| | - Marina De Tommaso
- Unità di Neurofisiopatologia del Dolore, Dipartimento di Scienze Mediche di Base, Neuroscienze e Organi di Senso (SMBNOS), Università degli Studi di Bari Aldo Moro, Bari, Italy
| | - Giuseppe Battaglia
- Dipartimento di Scienze Psicologiche, Pedagogiche, dell'Esercizio Fisico e della Formazione, Università degli Studi di Palermo, Palermo, Italy
| | | | - Giuliana Guggino
- Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), Università degli Studi di Palermo, Palermo, Italy
| | - Brigida Fierro
- Dipartimento di Biomedicina, Neuroscienze e Diagnostica Avanzata (BIND), Università degli Studi di Palermo, Palermo, Italy
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Moana-Filho EJ, Herrero Babiloni A. Endogenous pain modulation in chronic temporomandibular disorders: Derivation of pain modulation profiles and assessment of its relationship with clinical characteristics. J Oral Rehabil 2018; 46:219-232. [DOI: 10.1111/joor.12745] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2018] [Revised: 09/26/2018] [Accepted: 10/31/2018] [Indexed: 01/14/2023]
Affiliation(s)
- Estephan J. Moana-Filho
- Division of TMD & Orofacial Pain, School of Dentistry; University of Minnesota; Minneapolis Minnesota
| | - Alberto Herrero Babiloni
- Division of TMD & Orofacial Pain, School of Dentistry; University of Minnesota; Minneapolis Minnesota
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48
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Ness TJ, DeWitte C, DeBerry JJ, Randich A. Neonatal bladder inflammation alters the role of the central amygdala in hypersensitivity produced by Acute Footshock stress in adult female rats. Brain Res 2018; 1698:99-105. [PMID: 29964025 DOI: 10.1016/j.brainres.2018.06.030] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2017] [Revised: 05/26/2018] [Accepted: 06/28/2018] [Indexed: 01/11/2023]
Abstract
There is increasing evidence that chronic pain may be associated with events that occur during critical periods of development. Recent studies have identified behavioral, spinal neurophysiological and spinal/peripheral neurochemical differences in rats that have experienced neonatal bladder inflammation (NBI): a putative model of the chronically painful bladder disorder, interstitial cystitis. Stress has been shown to exacerbate symptoms of interstitial cystitis and produces bladder hypersensitivity in animal models. We recently reported that Acute Footshock-induced bladder hypersensitivity was eliminated in otherwise normal rats by prior bilateral lesions of the central nucleus of the amygdala. Since the spinal and peripheral nervous systems of NBI-treated rats are known to differ from normal rats, the present experiments sought to determine whether a supraspinal nervous system structure, the central amygdala, is still necessary for the induction of Acute Footshock-induced hypersensitivity. The effect of bilateral amygdala electrolytic lesions on Acute Footshock-induced bladder hypersensitivity in adult female rats was tested in Control rats which underwent a control protocol as neonates and in experimental rats which experienced NBI. Consistent with our previous report, in Control rats, Acute Footshock-induced bladder hypersensitivity was eliminated by bilateral Amygdala Lesions. In contrast, Acute Footshock-induced bladder hypersensitivity in NBI-treated rats was unaffected by bilateral Amygdala Lesions. These findings provide evidence that NBI results in the recruitment of substrates of bladder hypersensitivity that may differ from those of normal rats. This, in turn, suggests that unique therapeutics may be needed for painful bladder disorders like interstitial cystitis.
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Affiliation(s)
- Timothy J Ness
- Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
| | - Cary DeWitte
- Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America
| | - Jennifer J DeBerry
- Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America
| | - Alan Randich
- Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America
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49
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Ladouceur A, Rustamov N, Dubois JD, Tessier J, Lehmann A, Descarreaux M, Rainville P, Piché M. Inhibition of Pain and Pain-Related Brain Activity by Heterotopic Noxious Counter-Stimulation and Selective Attention in Chronic Non-Specific Low Back Pain. Neuroscience 2018; 387:201-213. [DOI: 10.1016/j.neuroscience.2017.09.054] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2017] [Revised: 09/26/2017] [Accepted: 09/28/2017] [Indexed: 12/22/2022]
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50
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Wickwire EM, Schnyer DM, Germain A, Williams SG, Lettieri CJ, McKeon AB, Scharf SM, Stocker R, Albrecht J, Badjatia N, Markowitz AJ, Manley GT. Sleep, Sleep Disorders, and Circadian Health following Mild Traumatic Brain Injury in Adults: Review and Research Agenda. J Neurotrauma 2018; 35:2615-2631. [PMID: 29877132 DOI: 10.1089/neu.2017.5243] [Citation(s) in RCA: 77] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
A rapidly expanding scientific literature supports the frequent co-occurrence of sleep and circadian disturbances following mild traumatic brain injury (mTBI). Although many questions remain unanswered, the preponderance of evidence suggests that sleep and circadian disorders can result from mTBI. Among those with mTBI, sleep disturbances and clinical sleep and circadian disorders contribute to the morbidity and long-term sequelae across domains of functional outcomes and quality of life. Specifically, along with deterioration of neurocognitive performance, insufficient and disturbed sleep can precede, exacerbate, or perpetuate many of the other common sequelae of mTBI, including depression, post-traumatic stress disorder, and chronic pain. Further, sleep and mTBI share neurophysiologic and neuroanatomic mechanisms that likely bear directly on success of rehabilitation following mTBI. For these reasons, focus on disturbed sleep as a modifiable treatment target has high likelihood of improving outcomes in mTBI. Here, we review relevant literature and present a research agenda to 1) advance understanding of the reciprocal relationships between sleep and circadian factors and mTBI sequelae and 2) advance rapidly the development of sleep-related treatments in this population.
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Affiliation(s)
- Emerson M Wickwire
- 1 Department of Psychiatry, University of Maryland School of Medicine , Baltimore, Maryland.,2 Sleep Disorders Center, Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Maryland School of Medicine , Baltimore, Maryland
| | - David M Schnyer
- 3 Department of Psychology, University of Texas , Austin, Texas
| | - Anne Germain
- 4 Department of Psychiatry, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania
| | - Scott G Williams
- 5 Sleep Disorders Center, Department of Medicine, Walter Reed National Military Medical Center , Bethesda, Maryland.,6 Department of Medicine, Uniformed Services University of the Health Sciences , Bethesda, Maryland
| | - Christopher J Lettieri
- 5 Sleep Disorders Center, Department of Medicine, Walter Reed National Military Medical Center , Bethesda, Maryland.,6 Department of Medicine, Uniformed Services University of the Health Sciences , Bethesda, Maryland
| | - Ashlee B McKeon
- 4 Department of Psychiatry, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania
| | - Steven M Scharf
- 2 Sleep Disorders Center, Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Maryland School of Medicine , Baltimore, Maryland
| | - Ryan Stocker
- 7 University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania
| | - Jennifer Albrecht
- 8 Department of Epidemiology and Public Health, University of Maryland School of Medicine , Baltimore, Maryland
| | - Neeraj Badjatia
- 9 Department of Neurology, University of Maryland School of Medicine , Baltimore, Maryland
| | - Amy J Markowitz
- 10 UCSF Brain and Spinal Injury Center , San Francisco, California
| | - Geoffrey T Manley
- 11 Department of Neurosurgery, University of California , San Francisco, California
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