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Relief of chronic pain associated with increase in midline frontal theta power. Pain Rep 2022; 7:e1040. [PMID: 36247110 PMCID: PMC9555895 DOI: 10.1097/pr9.0000000000001040] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 07/27/2022] [Accepted: 08/11/2022] [Indexed: 11/26/2022] Open
Abstract
Unique electroencephalogram signatures of relief from chronic pain demonstrate theta power increase in the midline frontal cortex. Introduction: Objectives: Methods: Results: Conclusion:
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Teel EF, Ocay DD, Blain-Moraes S, Ferland CE. Accurate classification of pain experiences using wearable electroencephalography in adolescents with and without chronic musculoskeletal pain. FRONTIERS IN PAIN RESEARCH 2022; 3:991793. [PMID: 36238349 PMCID: PMC9552004 DOI: 10.3389/fpain.2022.991793] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Accepted: 09/14/2022] [Indexed: 11/23/2022] Open
Abstract
Objective We assessed the potential of using EEG to detect cold thermal pain in adolescents with and without chronic musculoskeletal pain. Methods Thirty-nine healthy controls (15.2 ± 2.1 years, 18 females) and 121 chronic pain participants (15.0 ± 2.0 years, 100 females, 85 experiencing pain ≥12-months) had 19-channel EEG recorded at rest and throughout a cold-pressor task (CPT). Permutation entropy, directed phase lag index, peak frequency, and binary graph theory features were calculated across 10-second EEG epochs (Healthy: 292 baseline / 273 CPT epochs; Pain: 1039 baseline / 755 CPT epochs). Support vector machine (SVM) and logistic regression models were trained to classify between baseline and CPT conditions separately for control and pain participants. Results SVM models significantly distinguished between baseline and CPT conditions in chronic pain (75.2% accuracy, 95% CI: 71.4%–77.1%; p < 0.0001) and control (74.8% accuracy, 95% CI: 66.3%–77.6%; p < 0.0001) participants. Logistic regression models performed similar to the SVM (Pain: 75.8% accuracy, 95% CI: 69.5%–76.6%, p < 0.0001; Controls: 72.0% accuracy, 95% CI: 64.5%–78.5%, p < 0.0001). Permutation entropy features in the theta frequency band were the largest contributor to model accuracy for both groups. Conclusions Our results demonstrate that subjective pain experiences can accurately be detected from electrophysiological data, and represent the first step towards the development of a point-of-care system to detect pain in the absence of self-report.
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Affiliation(s)
- Elizabeth F. Teel
- Department of Health, Kinesiology, & Applied Physiology, School of Physical and Occupational Therapy, McGill University, Montreal, QC, Canada
| | - Don Daniel Ocay
- Department of Experimental Surgery, McGill University, Montreal, QC, Canada
- Shriners Hospitals for Children-Canada, Montreal, QC, Canada
| | - Stefanie Blain-Moraes
- Montreal General Hospital, McGill University Health Centre, Montreal, QC, Canada
- School of Physical and Occupational Therapy, McGill University, Montreal, QC, Canada
- Correspondence: Stefanie Blain-Moraes
| | - Catherine E. Ferland
- Shriners Hospitals for Children-Canada, Montreal, QC, Canada
- Montreal General Hospital, McGill University Health Centre, Montreal, QC, Canada
- Department of Anesthesia, McGill University, Montreal, QC, Canada
- Research Institute-McGill University Health Centre, Montreal, QC, Canada
- Alan Edwards Research Center for Pain, McGill University, Montreal, QC, Canada
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Gloeckner CD, Nocon JC, Lim HH. Topographic and widespread auditory modulation of the somatosensory cortex: potential for bimodal sound and body stimulation for pain treatment. J Neural Eng 2022; 19. [PMID: 35671702 DOI: 10.1088/1741-2552/ac7665] [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: 01/11/2022] [Accepted: 06/07/2022] [Indexed: 11/11/2022]
Abstract
OBJECTIVE There has been growing interest in understanding multisensory integration in the cortex through activation of multiple sensory and motor pathways to treat brain disorders, such as tinnitus or essential tremors. For tinnitus, previous studies show that combined sound and body stimulation can modulate the auditory pathway and lead to significant improvements in tinnitus symptoms. Considering that tinnitus is a type of chronic auditory pain, bimodal stimulation could potentially alter activity in the somatosensory pathway relevant for treating chronic pain. As an initial step towards that goal, we mapped and characterized neuromodulation effects in the somatosensory cortex (SC) in response to sound and/or electrical stimulation of the body. APPROACH We first mapped the topographic organization of activity across the SC of ketamine-anesthetized guinea pigs through electrical stimulation of different body locations using subcutaneous needle electrodes or with broadband acoustic stimulation. We then characterized how neural activity in different parts of the SC could be facilitated or suppressed with bimodal stimulation. MAIN RESULTS The topography in the SC of guinea pigs in response to electrical stimulation of the body aligns consistently to that shown in previous rodent studies. Interestingly, auditory broadband noise stimulation primarily excited SC areas that typically respond to stimulation of lower body locations. Although there was only a small subset of SC locations that were excited by acoustic stimulation alone, all SC recording sites could be altered (facilitated or suppressed) with bimodal stimulation. Furthermore, specific regions of the SC could be modulated by stimulating an appropriate body region combined with broadband noise. SIGNIFICANCE These findings show that bimodal stimulation can excite or modulate firing across a widespread yet targeted population of SC neurons. This approach may provide a non-invasive method for altering or disrupting abnormal firing patterns within certain parts of the SC for chronic pain treatment.
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Affiliation(s)
- Cory D Gloeckner
- University of Minnesota Duluth, 1305 Ordean Court, Duluth, Minnesota, 55812, UNITED STATES
| | - Jian C Nocon
- Biomedical Engineering, Boston University, 44 Cummington Mall, Boston, Massachusetts, 02215, UNITED STATES
| | - Hubert H Lim
- Department of Biomedical Engineering, University of Minnesota, 7-105 Hasselmo Hall, 312 Church Street SE, Minneapolis, MN 55455, USA, Minneapolis, Minnesota, 55455, UNITED STATES
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Unmitigated Surgical Castration in Calves of Different Ages: Electroencephalographic and Neurohormonal Findings. Animals (Basel) 2021; 11:ani11061791. [PMID: 34203947 PMCID: PMC8232710 DOI: 10.3390/ani11061791] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 06/11/2021] [Indexed: 11/17/2022] Open
Abstract
Castration is a common management procedure employed in North American cattle production and is known to cause a pain response. The present study was designed to investigate the effect of unmitigated surgical castration on the electroencephalography (EEG) responses and plasma substance P (SP) concentrations in calves of different ages under the same experimental conditions. Thirty male Holstein calves in three age categories [<6 weeks (6W); 3 months (3M); 6 months (6M); 10 calves per age group] were used in the study. Calves were subjected to a simulated castration session (SHAM) followed 24 h later by surgical castration (CAST) without analgesia. An EEG analysis was performed before the procedure (i.e., baseline), at treatment, and 0-5, 5-10, and 10-20 min post-treatment for both SHAM and CAST, respectively. Blood samples were collected immediately prior to both treatments (time 0) and again at 1, 2, 4, 8, and 12 h after both treatments. The EEG results showed a three-way interaction between treatment, age, and time for delta and beta absolute power, beta relative power, total power, and median frequency (p = 0.004, p = 0.04, p = 0.04, p = 0.03, and p = 0.008, respectively). Following CAST, EEG total power decreased, and median frequency increased relative to SHAM in 6W and 3M calves only following treatment. For 6W and 3M calves, delta and beta absolute power increased at CAST and at later time points relative to SHAM. Marginal evidence for two-way interactions was noted between time and treatment and between age and treatment on the concentration of SP (p = 0.068 and p = 0.066, respectively). Substance P concentrations decreased in CAST treatment compared to SHAM at the later times (8 h: p = 0.007; 12 h: p = 0.048); 6W calves showed lower SP concentration at CAST relative to SHAM (p = 0.017). These findings indicate variation in EEG responses and in SP concentrations following unmitigated surgical castration in calves and that these responses may be age specific. These EEG findings have implications for supporting the perception of the pain associated with surgical castration in young calves and emphasize the urgency of pain mitigation strategies during routine husbandry practices such as castration, as typically implemented in North American cattle management.
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Hippocampal oscillatory dynamics and sleep atonia are altered in an animal model of fibromyalgia: Implications in the search for biomarkers. J Comp Neurol 2020; 528:1367-1391. [DOI: 10.1002/cne.24829] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Revised: 11/26/2019] [Accepted: 11/27/2019] [Indexed: 11/07/2022]
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Alabi EB, Simpson TL. Pupil response to noxious corneal stimulation. PLoS One 2020; 15:e0227771. [PMID: 31951635 PMCID: PMC6968842 DOI: 10.1371/journal.pone.0227771] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Accepted: 12/27/2019] [Indexed: 11/17/2022] Open
Abstract
Purpose Ocular somatosensory-autonomic reflexes play critical roles in maintaining homeostasis of the eye. The purpose of this study was to investigate the pupil response to nociceptive corneal stimuli. Methods A Waterloo-Belmonte pneumatic esthesiometer was used to determine detection thresholds and randomly deliver mechanical and chemical stimuli from levels of detection threshold to twice the threshold in 50% steps to the central cornea of 15 healthy subjects. For each stimulus, imaging of the stimulated/unstimulated eye was performed using two modified/calibrated Logitech c920 digital cameras for 4 seconds each, pre/post stimulus capture. The data were processed with a custom segmentation algorithm to help identify the pupils and pupil diameter was measured using ImageJ software. Pupil dilation response differences between the ipsi- and contralateral eye was analyzed using dependent t-tests. The effect of stimulus intensity, modality and sex of subjects were analyzed using repeated measures. Results In mechanical and chemical stimulation experiments, there was no difference in pupil responses between the stimulated eye and the unstimulated eye, (all dependent T-test p > 0.05). On average, pupil diameter increased from baseline as the corneal stimulus intensity increased. This happened regardless of whether mechanical or chemical stimulation occurred (ANOVA p < 0.05). At 200% threshold, pupil diameter was greater than at all stimulus intensities (Tukey HSD, all p < 0.05). Based on stimulus intensity, females had greater pupil diameters than males at levels of 150% threshold and 200% threshold (ANOVA p < 0.05, all Tukey HSD p < 0.05). Conclusion This study serves as a basis for the characterization of the local stimulus-response neural circuitry relating nociceptive stimuli to autonomic responses and in combination with our work on completely separate autonomic circuits of bulbar conjunctival vessel dilation and reflex tearing suggests that the monotonic measurements of redness, tearing and pupils provide accurate, separable responses that reflect painful stimulus intensity.
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Affiliation(s)
- Emmanuel B Alabi
- University of Waterloo, School of Optometry and Vision Science, Waterloo, ON, Canada
| | - Trefford L Simpson
- University of Waterloo, School of Optometry and Vision Science, Waterloo, ON, Canada
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Does High Frequency Transcutaneous Electrical Nerve Stimulation (TENS) Affect EEG Gamma Band Activity? J Biomed Phys Eng 2018; 8:271-280. [PMID: 30320031 PMCID: PMC6169118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2017] [Accepted: 01/14/2018] [Indexed: 11/02/2022]
Abstract
BACKGROUND Transcutaneous electrical nerve stimulation (TENS) is a noninvasive, inexpensive and safe analgesic technique used for relieving acute and chronic pain. However, despite all these advantages, there has been very little research into the therapeutic effects of TENS on brain activity. To the best of our knowledge, there is no evidence on the effect of high frequency TENS on the gamma band activity. OBJECTIVE Investigation of the effect of high frequency TENS on the electroencephalographic (EEG) gamma band activity after inducing ischemic pain in healthy volunteers is considered. MATERIAL AND METHODS The modified version of Submaximal effort tourniquet test was carried out to induce tonic pain in 15 right-handed healthy volunteers. The high frequency TENS (150µs in duration, frequency of 100 Hz) was applied for 20 minutes. Pain intensity was assessed at using Visual Analog Scale (VAS) in two conditions (after-pain, after-TENS). EEG gamma band activity was recorded by a 19-channel EEG in three conditions (baseline, after-pain and after- TENS). The repeated measure ANOVA and paired-sample T- tests were used for data analysis. RESULTS EEG analysis showed an increase in gamma total power after inducing pain as compared to baseline and a decrease after the application of TENS (mean±SD: .043±.029 to .088±.042 to .038±.022 μV2 ).The analysis of VAS values demonstrated that the intensity of induced pain (mean±SD: 51.53±9.86) decreased after the application of TENS (mean±SD: 18.66±10.28). All these differences were statistically significant (p<.001). CONCLUSION The results of this study revealed that the high frequency TENS can reduce the enhanced gamma band activity after the induction of tonic pain in healthy volunteers. This finding might help as a functional brain biomarker which could be useful for pain treatment, specifically for EEG-based neurofeedback approaches.
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Hadjileontiadis LJ. EEG-Based Tonic Cold Pain Characterization Using Wavelet Higher Order Spectral Features. IEEE Trans Biomed Eng 2015; 62:1981-91. [PMID: 25769141 DOI: 10.1109/tbme.2015.2409133] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
A novel approach in tonic cold pain characterization, based on electroencephalograph (EEG) data analysis using wavelet higher order spectral (WHOS) features, is presented here. The proposed WHOS-based feature space extends the relative power spectrum-based (phase blind) approaches reported so far a step forward; this is realized via dynamic monitoring of the nonlinerities of the EEG brain response to tonic cold pain stimuli by capturing the change in the underlying quadratic phase coupling at the bifrequency wavelet bispectrum/bicoherence domain due to the change of the pain level. Three pain characterization scenarios were formed and experimentally tested involving WHOS-based analysis of EEG data, acquired from 17 healthy volunteers that were subjected to trials of tonic cold pain stimuli. The experimental and classification analysis results, based on four well-known classifiers, have shown that the WHOS-based features successfully discriminate relax from pain status, provide efficient identification of the transition from relax to mild and/or severe pain status, and translate the subjective perception of pain to an objective measure of pain endurance. These findings seem quite promising and pave the way for adopting WHOS-based approaches to pain characterization under other types of pain, e.g., chronic pain and various clinical scenarios.
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Abstract
Chronic pain is common, and the available treatments do not provide adequate relief for most patients. Neuromodulatory interventions that modify brain processes underlying the experience of pain have the potential to provide substantial relief for some of these patients. The purpose of this Review is to summarize the state of knowledge regarding the efficacy and mechanisms of noninvasive neuromodulatory treatments for chronic pain. The findings provide support for the efficacy and positive side-effect profile of hypnosis, and limited evidence for the potential efficacy of meditation training, noninvasive electrical stimulation procedures, and neurofeedback procedures. Mechanisms research indicates that hypnosis influences multiple neurophysiological processes involved in the experience of pain. Evidence also indicates that mindfulness meditation has both immediate and long-term effects on cortical structures and activity involved in attention, emotional responding and pain. Less is known about the mechanisms of other neuromodulatory treatments. On the basis of the data discussed in this Review, training in the use of self-hypnosis might be considered a viable 'first-line' approach to treat chronic pain. More-definitive research regarding the benefits and costs of meditation training, noninvasive brain stimulation and neurofeedback is needed before these treatments can be recommended for the treatment of chronic pain.
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Affiliation(s)
- Mark P Jensen
- Department of Rehabilitation Medicine, University of Washington, Harborview Medical Center, 325 9th Avenue, Seattle, WA 98104-2499, USA
| | - Melissa A Day
- Department of Rehabilitation Medicine, University of Washington, Harborview Medical Center, 325 9th Avenue, Seattle, WA 98104-2499, USA
| | - Jordi Miró
- Department of Psychology, Universitat Rovira i Virgili, Carretera de Valls, s/n, 43007 Tarragona, Spain
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Subjects’ hypnotizability level affects somatosensory evoked potentials to non-painful and painful stimuli. Clin Neurophysiol 2013; 124:1448-55. [DOI: 10.1016/j.clinph.2013.02.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2012] [Revised: 01/29/2013] [Accepted: 02/03/2013] [Indexed: 11/19/2022]
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童 基. The Research on Pain Mechanism Based on the Spectrum Analysis of EEG. Biophysics (Nagoya-shi) 2013. [DOI: 10.12677/biphy.2013.12004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
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Shao S, Shen K, Yu K, Wilder-Smith EPV, Li X. Frequency-domain EEG source analysis for acute tonic cold pain perception. Clin Neurophysiol 2012; 123:2042-9. [PMID: 22538122 DOI: 10.1016/j.clinph.2012.02.084] [Citation(s) in RCA: 78] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2011] [Revised: 02/01/2012] [Accepted: 02/02/2012] [Indexed: 11/30/2022]
Abstract
OBJECTIVE To investigate electrocortical responses to tonic cold pain by frequency-domain electroencephalogram (EEG) source analysis, and to identify potential electrocortical indices of acute tonic pain. METHODS Scalp EEG data were recorded from 26 healthy subjects under tonic cold pain (CP) and no-pain control (NP) conditions. EEG power spectra and the standardized low-resolution brain electromagnetic tomography (sLORETA) localized EEG cortical sources were compared between the two conditions in five frequency bands: 1-4 Hz, 4-8 Hz, 8-12 Hz, 12-18 Hz and 18-30 Hz. RESULTS In line with the EEG power spectral results, the source power significantly differed between the CP and NP conditions in 8-12 Hz (CP<NP) and 18-30 Hz (CP>NP) in extensive brain regions. Besides, there were also significantly different 4-8 Hz and 12-18 Hz source activities between the two conditions. Among the significant source activities, the left medial frontal and left superior frontal 4-8 Hz activities, the anterior cingulate 8-12 Hz activity and the posterior cingulate 12-18 Hz activity showed significant negative correlations with subjective pain ratings. CONCLUSIONS The brain's perception of tonic cold pain was characterized by cortical source power changes across different frequency bands in multiple brain regions. Oscillatory activities that significantly correlated with subjective pain ratings were found in the prefrontal and cingulate regions. SIGNIFICANCE These findings may offer useful measures for objective pain assessment and provide a basis for pain treatment by modulation of neural oscillations at specific frequencies in specific brain regions.
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Affiliation(s)
- Shiyun Shao
- Department of Mechanical Engineering, National University of Singapore, Singapore
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Shao S, Shen K, Wilder-Smith EP, Li X. Effect of pain perception on the heartbeat evoked potential. Clin Neurophysiol 2011; 122:1838-45. [DOI: 10.1016/j.clinph.2011.02.014] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2010] [Revised: 02/03/2011] [Accepted: 02/14/2011] [Indexed: 11/30/2022]
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Bergamasco L, Coetzee JF, Gehring R, Murray L, Song T, Mosher RA. Effect of intravenous sodium salicylate administration prior to castration on plasma cortisol and electroencephalography parameters in calves. J Vet Pharmacol Ther 2011; 34:565-76. [PMID: 21303378 DOI: 10.1111/j.1365-2885.2011.01269.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Nociception is an unavoidable consequence of many routine management procedures such as castration in cattle. This study investigated electroencephalography (EEG) parameters and cortisol levels in calves receiving intravenous sodium salicylate in response to a castration model. Twelve Holstein calves were randomly assigned to the following groups: (i) castrated, untreated controls, (ii) 50 mg/kg sodium salicylate IV precastration, were blood sampled at 0, 5, 10, 20, 30, 45, 60, 90, 120, 150, 180, 240, 360, and 480 min postcastration. The EEG recording included baseline, castration, immediate recovery (0-5 min after castration), middle recovery (5-10 min after castration), and late recovery (10-20 min after castration). Samples were analyzed by competitive chemiluminescent immunoassay and fluorescence polarization immunoassay for cortisol and salicylate, respectively. EEG visual inspection and spectral analysis were performed. Statistical analyses included anova repeated measures and correlations between response variable. No treatment effect was noted between the two groups for cortisol and EEG measurements, namely an attenuation of acute cortisol response and EEG desynchronization in sodium salicylate group. Time effects were noted for EEG measurements, cortisol and salicylates levels. Significant correlations between cortisol and EEG parameters were noted. These findings have implications for designing effective analgesic regimens, and they suggest that EEG can be useful to monitor pain attributable to castration.
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Affiliation(s)
- L Bergamasco
- Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, USA.
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Hargrove JB, Bennett RM, Simons DG, Smith SJ, Nagpal S, Deering DE. Quantitative electroencephalographic abnormalities in fibromyalgia patients. Clin EEG Neurosci 2010; 41:132-9. [PMID: 20722346 DOI: 10.1177/155005941004100305] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
There is increasing acceptance that pain in fibromyalgia (FM) is a result of dysfunctional sensory processing in the spinal cord and brain, and a number of recent imaging studies have demonstrated abnormal central mechanisms. The objective of this report is to statistically compare quantitative electroencephalogram (qEEG) measures in 85 FM patients with age and gender matched controls in a normative database. A statistically significant sample (minimum 60 seconds from each subject) of artifact-free EEG data exhibiting a minimum split-half reliability ratio of 0.95 and test-retest reliability ratio of 0.90 was used as the threshold for acceptable data inclusion. FM subject EEG data was compared to EEGs of age and gender matched healthy subjects in the Lifespan Normative Database and analyzed using NeuroGuide 2.0 software. Analyses were based on spectral absolute power, relative power and coherence. Clinical evaluations included the Fibromyalgia Impact Questionnaire (FIQ), Beck Depression Inventory and Fischer dolorimetry for pain pressure thresholds. Based on Z-statistic findings, the EEGs from FM subjects differed from matched controls in the normative database in three features: (1) reduced EEG spectral absolute power in the frontal International 10-20 EEG measurement sites, particularly in the low- to mid-frequency EEG spectral segments; (2) elevated spectral relative power of high frequency components in frontal/central EEG measurement sites; and (3) widespread hypocoherence, particularly in low- to mid-frequency EEG spectral segments, in the frontal EEG measurement sites. A consistent and significant negative correlation was found between pain severity and the magnitude of the EEG abnormalities. No relationship between EEG findings and medicine use was found. It is concluded that qEEG analysis reveals significant differences between FM patients compared to age and gender matched healthy controls in a normative database, and has the potential to be a clinically useful tool for assessing brain function in FM patients.
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Affiliation(s)
- Jeffrey B Hargrove
- Department of Medicine, Michigan State University College of Human Medicine, Kettering University, Flint, Michigan 48504, USA.
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Higher cortical modulation of pain perception in the human brain: Psychological determinant. Neurosci Bull 2010; 25:267-76. [PMID: 19784081 DOI: 10.1007/s12264-009-0918-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
Pain perception and its genesis in the human brain have been reviewed recently. In the current article, the reports on pain modulation in the human brain were reviewed from higher cortical regulation, i.e. top-down effect, particularly studied in psychological determinants. Pain modulation can be examined by gene therapy, physical modulation, pharmacological modulation, psychological modulation, and pathophysiological modulation. In psychological modulation, this article examined (a) willed determination, (b) distraction, (c) placebo, (d) hypnosis, (e) meditation, (f) qi-gong, (g) belief, and (h) emotions, respectively, in the brain function for pain modulation. In each, the operational definition, cortical processing, neuroimaging, and pain modulation were systematically deliberated. However, not all studies had featured the brain modulation processing but rather demonstrated potential effects on human pain. In our own studies on the emotional modulation on human pain, we observed that emotions could be induced from music melodies or pictures perception for reduction of tonic human pain, mainly in potentiation of the posterior alpha EEG fields, likely resulted from underneath activities of precuneous in regulation of consciousness, including pain perception. To sum, higher brain functions become the leading edge research in all sciences. How to solve the information bit of thinking and feeling in the brain can be the greatest challenge of human intelligence. Application of higher cortical modulation of human pain and suffering can lead to the progress of social humanity and civilization.
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New insights into neuromodulatory approaches for the treatment of pain. THE JOURNAL OF PAIN 2007; 9:193-9. [PMID: 18096437 DOI: 10.1016/j.jpain.2007.11.003] [Citation(s) in RCA: 61] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Received: 07/11/2007] [Revised: 10/23/2007] [Accepted: 11/01/2007] [Indexed: 11/22/2022]
Abstract
UNLABELLED Two lines of evidence about the association between the experience of pain and brain state (measured via electroencephalogram or EEG) have recently come to light. First, research from a number of sources suggests a link between brain EEG activity and the experience of pain. Specifically, this research suggests that the subjective experience of pain is associated with relatively lower amplitudes of slower wave (delta, theta, and alpha) activity and relatively higher amplitudes of faster wave (beta) activity. Second, there has been a recent increase in interest in interventions that impact the cortical neuromodulation of pain, including behavioral treatments (such as self-hypnosis training and neurofeedback) and both invasive and noninvasive brain stimulation. Although a direct causal link between experience of pain and brain activity as measured by EEG has not been established, the targeting of pain treatment at a cortical level by trying to affect EEG rhythms directly is an intriguing possibility. PERSPECTIVE Preliminary evidence suggests the possibility, which has not yet adequately tested or proven, that the experience of chronic pain is linked to cortical activity as assessed via an electroencephalogram. Support for this hypothesis would have important implications for understanding the mechanisms that underlie a number of pain treatments, and for developing new innovative treatments for chronic pain management.
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Babiloni C, Brancucci A, Capotosto P, Del Percio C, Romani GL, Arendt-Nielsen L, Rossini PM. Different modalities of painful somatosensory stimulations affect anticipatory cortical processes: A high-resolution EEG study. Brain Res Bull 2007; 71:475-84. [PMID: 17259016 DOI: 10.1016/j.brainresbull.2006.10.025] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2006] [Revised: 10/23/2006] [Accepted: 10/23/2006] [Indexed: 11/28/2022]
Abstract
Pain sensation is characterized by multiple features that allow to differentiate pricking, burning, aching, stinging, and electrical shock. These features are sub-served by neural pathways that might give flexibility and selectivity to the cerebral anticipatory processes. In this line, the present high-resolution electroencephalography (EEG) study tested the hypothesis that the anticipatory cortical processes are stronger for painful thermal (biologically relevant) than electrical ("artificial") stimuli with similar intensity. EEG data (128 electrodes) were recorded in normal subjects during the expectancy of painful electrical or laser stimuli (visual omitted stimulus paradigm; interval between two painful stimuli: 16s), delivered over the median nerve region of the right arm (nonpainful stimuli as controls). After each stimulus, the subject reported the perceived stimulus intensity. Surface Laplacian estimation of the EEG data spatially enhanced the anticipatory stimulus-preceding negativity (SPN), which reflects motivational relevance of the stimulus. Subjects perceived no difference in the intensity of the electrical versus laser stimuli in both painful and nonpainful conditions. However, the anticipatory SPN appeared over large scalp regions before painful laser but not electrical stimulation. The same was true for the nonpainful stimulations. The present results suggest that the motivational anticipatory cortical processes are induced by nonpainful and painful biologically/ecologically relevant laser stimuli rather than by "artificial" electrical stimuli with similar intensity.
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Affiliation(s)
- Claudio Babiloni
- Dipartimento di Fisiologia Umana e Farmacologia, Università La Sapienza, Rome, Italy.
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Drewes AM, Pedersen J, Reddy H, Rasmussen K, Funch-Jensen P, Arendt-Nielsen L, Gregersen H. Central sensitization in patients with non-cardiac chest pain: a clinical experimental study. Scand J Gastroenterol 2006; 41:640-9. [PMID: 16754535 DOI: 10.1080/00365520500442559] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Patients with non-cardiac chest pain (NNCP) suffer from unexplained and often intractable pain which can pose a major clinical problem. The aim of this study was to investigate nociceptive processing in NNCP patients and their response to experimentally acid-induced oesophageal hyperalgesia using a multimodal stimulation protocol. MATERIAL AND METHODS Ten highly selected patients with NCCP (mean age 43 years, 1 M) were compared with an age- and gender-matched group of 20 healthy subjects. After preconditioning, the distal oesophagus was painfully distended with a balloon using "impedance planimetry". This method assesses the luminal cross-sectional area of the oesophagus based on the electrical impedance of the fluid inside the balloon. The baseline distensions were done before and after pharmacological relaxation of the smooth muscle with 20 mg butylscopolamine. After baseline distensions, a series of up to 10 mechanical stimuli was performed (temporal summation). The stimulations were repeated after sensitization of the oesophagus induced by acid perfusion. The sensory intensities were assessed during the stimulations and the referred pain area was mapped. RESULTS At baseline distensions, no differences were seen between patients and controls before and after relaxation of the smooth muscles. The patients tolerated fewer repeated distensions than controls (4.8+/-0.5 versus 9.1+/-0.9; p=0.04) and had an increased size of the referred pain areas to the mechanical stimulations (32.9+/-6.2 versus 64.9+/-18.3 cm2; p=0.01). After sensitization with acid, the patients developed hyperalgesia (p<0.001), whereas no significant changes were seen in controls. CONCLUSIONS NCCP patients showed facilitated central pain mechanisms (temporal summation and visceral hyperalgesia after sensitization). This could be used in the diagnosis and understanding of the symptoms in these patients.
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Affiliation(s)
- Asbjørn Mohr Drewes
- Centre for Visceral Biomechanics and Pain, Department of Gastroenterology, Aalborg Hospital, Aalborg, Denmark.
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Drewes AM, Arendt-Nielsen L, Funch-Jensen P, Gregersen H. Experimental human pain models in gastro-esophageal reflux disease and unexplained chest pain. World J Gastroenterol 2006; 12:2806-17. [PMID: 16718803 PMCID: PMC4087795 DOI: 10.3748/wjg.v12.i18.2806] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Methods related to experimental human pain research aim at activating different nociceptors, evoke pain from different organs and activate specific pathways and mechanisms. The different possibilities for using mechanical, electrical, thermal and chemical methods in visceral pain research are discussed with emphasis of combinations (e.g., the multimodal approach). The methods have been used widely in assessment of pain mechanisms in the esophagus and have contributed to our understanding of the symptoms reported in these patients. Hence abnormal activation and plastic changes of central pain pathways seem to play a major role in the symptoms in some patients with gastro-esophageal reflux disease and in patients with functional chest pain of esophageal origin. These findings may lead to an alternative approach for treatment in patients that does not respond to conventional medical or surgical therapy.
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Affiliation(s)
- Asbjørn Mohr Drewes
- Center for Visceral Biomechanics and Pain, Department of Medical Gastroenterology, Aalborg University Hospital, DK-9000 Aalborg, Denmark.
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Al-Saadi MH, Nadeau V, Dickinson MR. A novel modelling and experimental technique to predict and measure tissue temperature during CO2 laser stimuli for human pain studies. Lasers Med Sci 2006; 21:95-100. [PMID: 16673053 DOI: 10.1007/s10103-006-0381-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2005] [Accepted: 03/13/2006] [Indexed: 11/29/2022]
Abstract
Laser nerve stimulation is now accepted as one of the preferred methods for applying painful stimuli to human skin during pain studies. One of the main concerns, however, is thermal damage to the skin. We present recent work based on using a CO2 laser with a remote infrared (IR) temperature sensor as a feedback system. A model for predicting the subcutaneous skin temperature derived from the signal from the IR detector allows us to accurately predict the laser parameters, thus maintaining an optimum pain stimulus whilst avoiding dangerous temperature levels, which could result in thermal damage. Another aim is to relate the modelling of the CO2 fibre laser interaction to the pain response and compare these results with practical measurements of the pain threshold for various stimulus parameters. The system will also allow us to maintain a constant skin temperature during the stimulus. Another aim of the experiments underway is to review the psychophysics for pain in human subjects, permitting an investigation of the relationship between temperature and perceived pain.
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Affiliation(s)
- Mohammed Hamed Al-Saadi
- Laser Photonics Group, School of Physics and Astronomy, University of Manchester, Manchester, M13 9PL, UK.
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Babiloni C, Brancucci A, Capotosto P, Arendt-Nielsen L, Chen ACN, Rossini PM. Expectancy of Pain Is Influenced by Motor Preparation: A High-Resolution EEG Study of Cortical Alpha Rhythms. Behav Neurosci 2005; 119:503-11. [PMID: 15839796 DOI: 10.1037/0735-7044.119.2.503] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
This high-resolution electroencephalographic (EEG) study on alpha event-related desynchronization (ERD) evaluated whether anticipatory activity precedes a sensorimotor interaction induced by concomitant painful stimuli and sensorimotor demand. An omitted-stimulus paradigm induced the expectancy of the painful stimulation at the left hand. In the experimental condition, the painful stimulation was associated with a visual go/no-go task triggering right-hand movements. Two control conditions manipulated the painful sensorimotor interaction variable. Compared with the control conditions, the expectancy of the painful sensorimotor interaction increased the high-band alpha EEG oscillations over the right primary sensorimotor cortex contralateral to the nociceptive stimuli and, to a lesser extent, over the centroparietal midline. These findings suggest that concomitant painful stimuli and simple sensorimotor go/no-go demands affect anticipatory activity as revealed by alpha ERD.
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Affiliation(s)
- Claudio Babiloni
- Dipartimento di Fisiologia Umana e Farmacologia, Università degli Studi di Roma La Sapienza, Rome, Italy.
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24
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Babiloni C, Brancucci A, Pizzella V, Romani GL, Tecchio F, Torquati K, Zappasodi F, Arendt-Nielsen L, Chen ACN, Rossini PM. Contingent Negative Variation in the Parasylvian Cortex Increases During Expectancy of Painful Sensorimotor Events: A Magnetoencephalographic Study. Behav Neurosci 2005; 119:491-502. [PMID: 15839795 DOI: 10.1037/0735-7044.119.2.491] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Previous evidence relating to somatosensory-evoked magnetic fields has shown that the human parasylvian cortex (PC) is affected by ongoing painful sensorimotor interactions. In the present magnetoencephalographic study, the activity of the PC was investigated to evaluate the hypothesis of anticipatory processes preceding painful sensorimotor interactions. Sensorimotor interactions were induced by warned painful electrical stimulations at the left hand concomitant with a motor task of the right hand. The anticipatory activity of the PC was probed via contingent negative variation. Compared with the control nonpainful condition, the anticipation of the painful sensorimotor interactions increased the PC activity over the hemisphere ipsilateral to the stimulation. Dipole modeling indicated that the center of gravity of the anticipatory activity in the PC was located in the secondary somatosensory cortex. These results suggest that anticipation of painful sensorimotor interactions engages the human PC, especially in the hemisphere ipsilateral to upcoming painful stimuli and contralateral to preparatory motor commands.
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Affiliation(s)
- Claudio Babiloni
- Dipartimento di Fisiologia Umana e Farmacologia, Università degli Studi di Roma La Sapienza, Rome, Italy.
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Abstract
Quantitative electroencephalogram (qEEG) plays a significant role in EEG-based clinical diagnosis and studies of brain function. In past decades, various qEEG methods have been extensively studied. This article provides a detailed review of the advances in this field. qEEG methods are generally classified into linear and nonlinear approaches. The traditional qEEG approach is based on spectrum analysis, which hypothesizes that the EEG is a stationary process. EEG signals are nonstationary and nonlinear, especially in some pathological conditions. Various time-frequency representations and time-dependent measures have been proposed to address those transient and irregular events in EEG. With regard to the nonlinearity of EEG, higher order statistics and chaotic measures have been put forward. In characterizing the interactions across the cerebral cortex, an information theory-based measure such as mutual information is applied. To improve the spatial resolution, qEEG analysis has also been combined with medical imaging technology (e.g., CT, MR, and PET). With these advances, qEEG plays a very important role in basic research and clinical studies of brain injury, neurological disorders, epilepsy, sleep studies and consciousness, and brain function.
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Affiliation(s)
- Nitish V Thakor
- Biomedical Engineering Department, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
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Staahl C, Drewes AM. Experimental Human Pain Models: A Review of Standardised Methods for Preclinical Testing of Analgesics. ACTA ACUST UNITED AC 2004; 95:97-111. [PMID: 15447733 DOI: 10.1111/j.1742-7843.2004.950301.x] [Citation(s) in RCA: 116] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Treatment of pain is one of the major challenges in clinical medicine. However, it is often difficult to evaluate the effect of a treatment, as the many symptoms of the underlying diseases often confound this assessment. Furthermore, as the pain mechanisms in many diseases are poorly understood, the limited successful trial and error approach is most often used in the selection of analgesics. Hence, there is a need for new methods in the characterization and treatment of pain. Human experimental pain models offer the possibility to explore the pain system under controlled settings. The models can also be used to screen the analgesic profiles of drugs targeted to treat pain. This review gives a brief introduction to the methods used to evoke and assess pain in the skin, muscle and viscera. New methods using multimodal stimulation and activation of central pain mechanisms can to a higher degree mimic the clinical situation, and such methods are recommended in the future screening of analgesics. Examples of the use of experimental pain models in the testing of analgesics are given. With these models the therapeutic spectrum may be defined from a differentiated knowledge on the effect of drugs on the pain system. Such information may be used in the future guidelines for trials and clinical use of analgesics.
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Affiliation(s)
- Camilla Staahl
- Centre for Visceral Biomechanics and Pain, Department of Medical Gastroenterology, University Hospital Aalborg, Denmark.
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27
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Babiloni C, Brancucci A, Babiloni F, Capotosto P, Carducci F, Cincotti F, Arendt-Nielsen L, Chen ACN, Rossini PM. Anticipatory cortical responses during the expectancy of a predictable painful stimulation. A high-resolution electroencephalography study. Eur J Neurosci 2003; 18:1692-700. [PMID: 14511347 DOI: 10.1046/j.1460-9568.2003.02851.x] [Citation(s) in RCA: 72] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
In the present study, high-resolution electroencephalography techniques modelled the spatiotemporal pattern of human anticipatory cortical responses preceding expected galvanic painful stimuli (non-painful stimuli as a control). Do these responses reflect the activation of associative other than somatosensory systems? Anticipatory processes were probed by alpha oscillations (6-12 Hz) for the evaluation of thalamocortical channels and by negative event-related potentials for the evaluation of cortical excitability. Compared with the control condition, a progressive reduction of the alpha power was recognized over the primary somatosensory cortex from 2 s before the painful stimulation. In contrast, the anticipatory event-related potentials were negligible during the expectancy period. The results on the alpha power suggest that the expectancy of the painful stimulation specifically facilitated the somatosensory thalamocortical channel. Remarkably, the associative frontal-parietal areas were not involved, possibly due to the predictable and repetitive features of the painful stimulus. The present results also suggest that negative event-related potentials are modest preceding warned stimuli (even if painful) with a simple information content.
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Affiliation(s)
- Claudio Babiloni
- Dipartimento di Fisiologia Umana e Farmacologia, Sezione di EEG ad Alta Risoluzione, Università degli Studi di Roma La Sapienza, P. le Aldo Moro 5, 00185 Rome, Italy.
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28
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Rössel P, Arendt-Nielsen L, Niddam D, Chen ACN, Drewes AM. Short latency cerebral response evoked by painful electrical stimulation applied to the human sigmoid colon and to the convergent referred somatic pain area. Exp Brain Res 2003; 151:115-22. [PMID: 12712308 DOI: 10.1007/s00221-003-1484-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2002] [Accepted: 03/18/2003] [Indexed: 01/07/2023]
Abstract
Background. The brain-gut interaction is important for the understanding of pain mechanisms related to gastroenterological diseases. Unfortunately little is known about the early cerebral events related to the processing of gut-evoked pain. The aims of this human study were (1) to investigate the early-evoked brain potentials (EPs) to painful sigmoid colon stimulation and (2) to evaluate the EPs evoked from the convergent referred skin pain area after this area was induced by the painful gut stimulation. The background for the second aim was to evaluate whether the convergent input between somatic and visceral structures could induce detectable short-term cortical reorganization. Methods. Eleven subjects (nine men) participated; the mean age was 39.5+/-11.9 years. The gut-evoked EPs (recorded from 31 scalp sites) were evoked by electrical stimulation 30 cm from the anal verge by a modified biopsy forceps, inserted through a sigmoidoscope. The painful gut stimulation elicited a characteristic pain pattern referred to the abdomen. The short latency somatosensory evoked potentials were evoked from the skin inside and outside the referred pain area elicited by gut stimulation. A total of 750 electrical stimuli were delivered to the gut at slight painful stimulus intensity and 500 stimuli were delivered to the skin. Results. Short-latency EPs to electrical gut stimulation with an onset of 50-60 ms could be recorded. The gut EP topography revealed three consecutive positive peaks (P63, P101, P145) towards the frontal area. Centroparietal negativities (N128 and N222) were found, which were followed by two central positivities (P269 and P352). The somatic and gut evoked EPs differed in morphology and topography, but the EPs to skin stimulation inside and outside the gut-evoked referred pain area did not differ significantly. Conclusion. Short latency (50-60 ms) EPs to painful electrical sigmoid colon stimulation were demonstrated, reflecting an early cortical processing of sensory input from the sigmoid colon. The early cortical processing of somatic input from experimentally evoked visceral referred pain areas did not cause any detectable short-term cortical reorganization.
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Affiliation(s)
- Petra Rössel
- Laboratory for Visceral Pain and Biomechanics, Department of Medical Gastroenterology, Aalborg Hospital, 9000 Aalborg, Denmark
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29
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30
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Chang PF, Arendt-Nielsen L, Chen ACN. Dynamic changes and spatial correlation of EEG activities during cold pressor test in man. Brain Res Bull 2002; 57:667-75. [PMID: 11927371 DOI: 10.1016/s0361-9230(01)00763-8] [Citation(s) in RCA: 108] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
To explore the effects of tonic cold pain in man, the pain rating (intensity and distress), skin temperature, and continuous EEG recording were conducted before, during, and after cold pressor test (CPT) in 15 young healthy males. The acquired electroencephalogram (EEG) data was analysed in four ways: (1) comparison of EEG topographic patterns and power spectra across baseline, CPT, and post-CPT; (2) dynamic EEG changes during CPT; (3) correlation of EEG activities at the isolated focal maxima across the three experimental stages; and (4) spatial correlation of EEG powers among the focal sites during CPT. Compared to baseline, CPT induced significant differences in EEG topographic patterns and power spectra, which showed the following characteristics. (A) The delta and theta activities increased in frontal areas with maxima at F8. (B) The alpha activities decreased in the posterior part of the head with maxima at POz. (C) The beta activities increased in the peripheral bi-temporal regions. (D) The decrease of alpha and increase of beta activities occurred immediately after the onset of CPT, but the increase of delta activity showed a relatively gradual process. (E) Individual consistency was significantly observed in delta power at F8 and alpha-1 power at POz across the stages. (F) Two independent spatial clusters of EEG activation, fronto-temporal delta-theta-beta activities and posterior parietal alpha activities emerged during CPT. This new evidence and the detailed EEG effects in CPT may enhance our understanding of the dynamics in cerebral processing of tonic noxious information. Alpha reduction may reflect the attention processing in nociceptive input, and the delta/theta/beta activation may be related to the motivational modulation of the brain.
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Affiliation(s)
- Peng Fei Chang
- Human Brain Mapping and Cortical Imaging Laboratory, Center for Sensory-Motor Interaction, Aalborg University, Fredrik Bajers Vej 7-D3, DK 9220 Aalborg, Denmark
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Babiloni C, Babiloni F, Carducci F, Cincotti F, Rosciarelli F, Arendt-Nielsen L, Chen ACN, Rossini PM. Human brain oscillatory activity phase-locked to painful electrical stimulations: a multi-channel EEG study. Hum Brain Mapp 2001; 15:112-23. [PMID: 11835602 PMCID: PMC6872083 DOI: 10.1002/hbm.10013] [Citation(s) in RCA: 64] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
The main aims of this study were 1) a fine spatial analysis of electroencephalographic (EEG) oscillations after galvanic painful stimulation (nonpainful stimulation as a reference) and 2) a comparative evaluation of phase- and nonphase-locked component of these EEG oscillations. Preliminary surface Laplacian transformation of EEG data (31 channels) reduced head volume conductor effects. EEG phase values were computed by FFT analysis and the statistical evaluation of these values was performed by Rayleigh test (P < 0.05). About 50% of the EEG single trials presented statistically the same FFT phase value of the evoked EEG oscillations (phase-locked single trials), indicating a preponderant phase-locked compared to nonphase-locked component. The remaining single trials showed random FFT phase values (nonphase-locked single trials), indicating a preponderant nonphase-locked compared to phase-locked component. Compared to nonpainful stimulation, painful stimulation increased phase-locked theta to gamma band responses in the contralateral hemisphere and decreased the phase-locked beta band response in the ipsilateral hemisphere. Furthermore, nonphase-locked alpha band response decreased in the ipsilateral fronto-central area. In conclusion, both decreased and increased EEG oscillatory responses to galvanic painful stimulation would occur in parallel in different cortical regions and in the phase- and nonphase-locked EEG data sets. This enriches the actual debate on the mapping of event-related oscillatory activity of human brain.
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Affiliation(s)
- Claudio Babiloni
- Dipartimento di Fisiologia Umana e Farmacologia, Università di Roma "La Sapienza," Rome, Italy.
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32
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Abstract
With the maturation of EEG/MEG brain mapping and PET/fMRI neuroimaging in the 1990s, greater understanding of pain processing in the brain now elucidates and may even challenge the classical theory of pain mechanisms. This review scans across the cultural diversity of pain expression and modulation in man. It outlines the difficulties in defining and studying human pain. It then focuses on methods of studying the brain in experimental and clinical pain, the cohesive results of brain mapping and neuroimaging of noxious perception, the implication of pain research in understanding human consciousness and the relevance to clinical care as well as to the basic science of human psychophysiology. Non-invasive brain studies in man start to unveil the age-old puzzles of pain-illusion, hypnosis and placebo in pain modulation. The neurophysiological and neurohemodynamic brain measures of experimental pain can now largely satisfy the psychophysiologist's dream, unimaginable only a few years ago, of modelling the body-brain, brain-mind, mind-matter duality in an inter-linking 3-P triad: physics (stimulus energy); physiology (brain activities); and psyche (perception). For neuropsychophysiology greater challenges lie ahead: (a) how to integrate a cohesive theory of human pain in the brain; (b) what levels of analyses are necessary and sufficient; (c) what constitutes the structural organisation of the pain matrix; (d) what are the modes of processing among and across the sites of these structures; and (e) how can neural computation of these processes in the brain be carried out? We may envision that modular identification and delineation of the arousal-attention, emotion-motivation and perception-cognition neural networks of pain processing in the brain will also lead to deeper understanding of the human mind. Two foreseeable impacts on clinical sciences and basic theories from brain mapping/neuroimaging are the plausible central origin in persistent pain and integration of sensory-motor function in pain perception.
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Affiliation(s)
- A C Chen
- Aalborg University, Aalborg, Denmark.
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Chang PF, Arendt-Nielsen L, Graven-Nielsen T, Svensson P, Chen AC. Topographic effects of tonic cutaneous nociceptive stimulation on human electroencephalograph. Neurosci Lett 2001; 305:49-52. [PMID: 11356305 DOI: 10.1016/s0304-3940(01)01802-x] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
To examine the specific effects of cutaneous pain on electroencephalographic (EEG) activities, tonic painful and non-painful sensations in left forearm were induced by intradermal injection of capsaicin 100 microg/20microl and the same volume of vehicle, respectively, in 15 healthy males. The EEG data acquired in five experimental conditions: (i) baseline A; (ii) non-painful vehicle injection; (iii) baseline B; (iv) painful capsaicin injection and (v) waning pain, were analyzed and compared with analysis of variance. Only the painful capsaicin injection evoked significant decreases of theta, alpha-1 and alpha-2 powers over the centro-parieto-occipital regions compared with baseline B. No significant difference in EEG activation between the non-painful vehicle injection and painful capsaicin injection was found. This implicates that the observed topographic EEG activation is not specific for pain but probably related to the cutaneous stimulation.
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Affiliation(s)
- P F Chang
- Human Brain Mapping and Cortical Imaging Laboratory, Center for Sensory-Motor Interaction, Aalborg University, Fredrik Bajers Vej 7 D-3 DK-9220, Aalborg, Denmark
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Rainero I, Amanzio M, Vighetti S, Bergamasco B, Pinessi L, Benedetti F. Quantitative EEG responses to ischaemic arm stress in migraine. Cephalalgia 2001; 21:224-9. [PMID: 11442558 DOI: 10.1046/j.1468-2982.2001.00209.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Several studies suggest that patients with migraine respond physiologically to stress differently from controls, yet experimental data are scarce. In order to evaluate the reactivity to stress in migraine, we recorded the quantitative electroencephalogram (qEEG) during non-noxious and noxious ischaemic arm stress in two groups of healthy controls and compared the results with the effects of non-noxious ischaemic arm stress in a group of patients with migraine. In the controls, non-noxious mild stress did not produce any qEEG change but noxious stress induced a significant decrease of the alpha power. By contrast, in migraine patients the non-noxious mild stress was sufficient to induce a significant decrease of the alpha power in all brain regions. The results of our study show that migraine sufferers display a lower threshold to physical stress and confirm previous studies indicating that migraine is a disease characterized by a state of altered neuronal excitability.
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Affiliation(s)
- I Rainero
- Neurology II -- Headache Center, Department of Neuroscience, University of Turin Medical School, Torino, Italy.
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35
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Babiloni C, Babiloni F, Carducci F, Cincotti F, Rosciarelli F, Rossini P, Arendt-Nielsen L, Chen A. Mapping of early and late human somatosensory evoked brain potentials to phasic galvanic painful stimulation. Hum Brain Mapp 2001; 12:168-79. [PMID: 11170308 PMCID: PMC6871996 DOI: 10.1002/1097-0193(200103)12:3<168::aid-hbm1013>3.0.co;2-o] [Citation(s) in RCA: 63] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
In the present study, we modeled the spatiotemporal evolution of human somatosensory evoked cortical potentials (SEPs) to brief median-nerve galvanic painful stimulation. SEPs were recorded (-50 to +250 ms) from 12 healthy subjects following nonpainful (reference), slight painful, and moderate painful stimulations (subjective scale). Laplacian transformation of scalp SEPs reduced head volume conduction effects and annulled electric reference influence. Typical SEP components to the galvanic nonpainful stimulation were contralateral frontal P20-N30-N60-N120-P170, central P22-P40, and parietal N20-P30-P60-P120 (N = negativity, P = positivity, number = latency in ms). These components were observed also with the painful stimulations, the N60, N120, P170 having a longer latency with the painful than nonpainful stimulations. Additional SEP components elicited by the painful stimulations were parietomedian P80 as well as central N125, P170 (cP170), and P200. These additional SEP components included the typical vertex negative-positive complex following transient painful stimulations. Latency of the SEP components exclusively elicited by painful stimulation is highly compatible with the involvement of A delta myelinated fibers/spinothalamic pathway. The topography of these components is in line with the response of both nociceptive medial and lateral systems including bilateral primary sensorimotor and anterior cingulate cortical areas. The role of attentive, affective, and motor aspects in the modulation of the reported SEP components merits investigation in future experiments.
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Affiliation(s)
- C Babiloni
- Dipartimento di Fisiologia Umana e Farmacologia, Universitá di Roma "La Sapienza," Roma, Italy.
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Stevens A, Batra A, Kötter I, Bartels M, Schwarz J. Both pain and EEG response to cold pressor stimulation occurs faster in fibromyalgia patients than in control subjects. Psychiatry Res 2000; 97:237-47. [PMID: 11166094 DOI: 10.1016/s0165-1781(00)00223-7] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Pain-evoked brain potentials elicited by laser stimulation have been repeatedly shown to be abnormal in fibromyalgia syndrome. However, to our knowledge this is the first study assessing enduring (cold pressor) pain and correlated EEG changes in fibromyalgia. EEG power and subjective pain ratings during the cold pressor test were analyzed and contrasted with tasks not involving sensory stimulation (rest, mental arithmetic and pain imagery) in 20 patients with fibromyalgia and 21 healthy control subjects. Fibromyalgia patients both perceived pain and judged pain as intolerable earlier than control subjects, while pain intensity ratings and EEG power changes during subjective awareness of pain were similar in both groups. In patients and control subjects, pain was correlated with a rise in delta, theta and beta power. EEG power spectra during pain imagery and mental arithmetic were significantly different from those observed during the cold pressor test. In conclusion, fibromyalgia patients seem to process painful stimuli abnormally in a quantitative sense, thus producing both the sensation of pain, as well as the associated EEG patterns, much earlier than control subjects. However, the quality of the pain-associated EEG changes seems similar.
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Affiliation(s)
- A Stevens
- Department of Psychiatry, University of Tübingen, Universitätsklinik für Psychiatrie und Psychotherapie, Osianderstr. 24, 72076, Tübingen, Germany.
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Le Pera D, Svensson P, Valeriani M, Watanabe I, Arendt-Nielsen L, Chen AC. Long-lasting effect evoked by tonic muscle pain on parietal EEG activity in humans. Clin Neurophysiol 2000; 111:2130-7. [PMID: 11090762 DOI: 10.1016/s1388-2457(00)00474-0] [Citation(s) in RCA: 40] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
OBJECTIVE To explore EEG changes evoked by tonic experimental muscle pain compared to a non-painful vibratory stimulus. METHODS Thirty-one EEG channels were recorded before, during and after painful and non-painful stimulation. Pain was induced in the left brachioradialis muscle by injection of hypertonic (5%) saline. The vibratory stimulus was applied to the skin area overlying the brachioradialis muscle. The power of the major frequency components of the EEG activity (FFT, fast Fourier transform) was quantified and t-maps between the different experimental conditions were evaluated in frequency domain. RESULTS The main effect of muscle pain, compared to non-painful stimulation, was a significant and long-lasting increase of delta (1-3 Hz) power and an alpha-1 (9-11 Hz) power increase over the contralateral parietal locus. This finding could suggest a decreased excitability of the primary somatosensory cortex during muscle pain. The main effect of vibration, compared to its unstimulated baseline, consisted in an increase of beta-1 (14-20 Hz) power in the right frontal region. CONCLUSIONS Our data demonstrate significant and specific topographic EEG changes during tonic muscle pain. Since these modifications differ from those produced by an unstimulated baseline and during non-painful tonic stimulation, they might reflect mechanisms involved in the processing of nociceptive and adverse tonic stimuli.
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Affiliation(s)
- D Le Pera
- Laboratory for Experimental Pain Research, Center for Sensory-Motor Interaction, Aalborg University, Aalborg, Denmark.
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Treede RD, Apkarian VA, Bromm B, Greenspan JD, Lenz FA. Cortical representation of pain: functional characterization of nociceptive areas near the lateral sulcus. Pain 2000; 87:113-119. [PMID: 10924804 DOI: 10.1016/s0304-3959(00)00350-x] [Citation(s) in RCA: 198] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Many lines of evidence implicate the somatosensory areas near the lateral sulcus (Sylvian fissure) in the cortical representation of pain. Anatomical tracing studies in the monkey show nociceptive projection pathways to the vicinity of the secondary somatosensory cortex in the parietal operculum, and to anterior parts of insular cortex deep inside the Sylvian fissure. Clinical observations demonstrate alterations in pain sensation following lesions in these two areas in human parasylvian cortex. Imaging studies in humans reveal increased blood flow in parasylvian cortex, both contralaterally and ipsilaterally, in response to painful stimuli. Painful stimuli (such as laser radiant heat) evoke potentials with a scalp maximum at anterior temporal positions (T3 and T4). Several dipole source analyses as well as subdural recordings have confirmed that the earliest evoked potential following painful laser stimulation of the skin derives from sources in the parietal operculum. Thus, imaging and electrophysiological studies in humans suggest that parasylvian cortex is activated by painful stimuli, and is one of the first cortical relay stations in the central processing of these stimuli. There is mounting evidence for closely located but separate representations of pain (deep parietal operculum and anterior insula) and touch (secondary somatosensory cortex and posterior insula) in parasylvian cortex. This anatomical separation may be one of the reasons why single unit recordings of nociceptive neurons are scarce within regions comprising low-threshold mechanoreceptive neurons. The functional significance (sensory-discriminative, affective-motivational, cognitive-evaluative) of the closely spaced parasylvian cortical areas in acute and chronic pain is only poorly understood. It is likely that some of these areas are involved in sensory-limbic projection pathways that may subserve the recognition of potentially tissue damaging stimuli as well as pain memory.
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Affiliation(s)
- Rolf-Detlef Treede
- Institute of Physiology and Pathophysiology, Johannes-Gutenberg-University, Saarstrasse 21, D-55099 Mainz, Germany State University of New York, Syracuse, NY, USA University Hospital Eppendorf, Hamburg, Germany University of Maryland, Baltimore, MD, USA Johns Hopkins Medical Institutions, Baltimore, MD, USA
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Syrovegin AV, Kukushkin ML, Gnezdilov AV, Reshetnyak VK, Ovechkin AM, Ivanov AM, Li TS. Changes in somatosensory evoked potentials and reflectory reactions of human hand muscles to nociceptive stimulation of index finger before and during ischemia. Bull Exp Biol Med 2000. [DOI: 10.1007/bf02433888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Jones AK. The contribution of functional imaging techniques to our understanding of rheumatic pain. Rheum Dis Clin North Am 1999; 25:123-52. [PMID: 10083962 DOI: 10.1016/s0889-857x(05)70058-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The main cerebral components of the human pain matrix have been defined using functional imaging techniques. The experience of pain is likely to be elaborated as a result of parallel processing within this matrix. There is not, therefore, a single pain center. The determinants of pain are as likely to be determined by top-down as by bottom-up processes. The precise function of the different components of the matrix are just beginning to be defined. There appear to be important adaptive responses in the forebrain components of the matrix during arthritic pain. Endogenous opioid peptides are strong candidates for the modulation of some of these responses. More extensive and sequential behavioral and functional imaging studies are required to establish the contribution these adaptive responses make to the perception of pain.
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Affiliation(s)
- A K Jones
- Human Physiology and Pain Research Laboratory, University of Manchester Rheumatic Diseases Centre, Hope Hospital, Salford, United Kingdom
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41
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Tölle TR, Kaufmann T, Siessmeier T, Lautenbacher S, Berthele A, Munz F, Zieglgänsberger W, Willoch F, Schwaiger M, Conrad B, Bartenstein P. Region-specific encoding of sensory and affective components of pain in the human brain: a positron emission tomography correlation analysis. Ann Neurol 1999; 45:40-7. [PMID: 9894875 DOI: 10.1002/1531-8249(199901)45:1<40::aid-art8>3.0.co;2-l] [Citation(s) in RCA: 254] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Brain imaging with positron emission tomography has identified some of the principal cerebral structures of a central network activated by pain. To discover whether the different cortical and subcortical areas process different components of the multidimensional nature of pain, we performed a regression analysis between noxious heat-related regional blood flow increases and experimental pain parameters reflecting detection of pain, encoding of pain intensity, as well as pain unpleasantness. The results of our activation study indicate that different functions in pain processing can be attributed to different brain regions; ie, the gating function reflected by the pain threshold appeared to be related to anterior cingulate cortex, the frontal inferior cortex, and the thalamus, the coding of pain intensity to the periventricular gray as well as to the posterior cingulate cortex, and the encoding of pain unpleasantness to the posterior sector of the anterior cingulate cortex.
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Affiliation(s)
- T R Tölle
- Department of Neurology, Technical University, Munich, Germany
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42
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Bromm B, Lorenz J. Neurophysiological evaluation of pain. ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY 1998; 107:227-53. [PMID: 9872441 DOI: 10.1016/s0013-4694(98)00075-3] [Citation(s) in RCA: 276] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Neurophysiological techniques for the evaluation of pain in humans have made important advances in the last decade. A number of features of neuroanatomy and physiology of nociception qualifies pain as a multidimensional phenomenon which is rather unique among the sensory systems and which poses a number of technical and procedural requirements for its appropriate diagnostic assessment. Various stimulation techniques to induce defined pain in humans and used in combination with the methodology of evoked electrical brain potentials and magnetic fields are presented. Most recent knowledge gathered from scalp topography and dipole source analysis of pain-relevant evoked potentials and fields is discussed. Particular emphasis is put upon laser-evoked potentials and their application for diagnosis, pathophysiological description and monitoring of patients with neurological disorders and abnormal pain states. Future perspectives in this growing field of research are discussed briefly.
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Affiliation(s)
- B Bromm
- Institute for Physiology, University Hospital Eppendorf, Hamburg, Germany
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Pillemer SR, Bradley LA, Crofford LJ, Moldofsky H, Chrousos GP. The neuroscience and endocrinology of fibromyalgia. ARTHRITIS AND RHEUMATISM 1997; 40:1928-39. [PMID: 9365080 DOI: 10.1002/art.1780401103] [Citation(s) in RCA: 170] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Affiliation(s)
- S R Pillemer
- National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892-6500, USA
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44
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Lutzenberger W, Flor H, Birbaumer N. Enhanced dimensional complexity of the EEG during memory for personal pain in chronic pain patients. Neurosci Lett 1997; 226:167-70. [PMID: 9175593 DOI: 10.1016/s0304-3940(97)00268-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Associative connections between cortical cell assemblies representing pain-related memories should be stronger and more extensive in subjects with chronic pain. To test this hypothesis, the dimensional complexity of the electroencephalograph (EEG) was examined during the actual experience as well as during memory for pain. Nine chronic pain patients and nine matched healthy controls participated in the study. During acute pain induction, acute pain recall, personal stress and pain recall, the EEG was recorded from 15 scalp sites. Non-linear analysis, based on the theory of deterministic chaos, revealed higher and more widespread EEG complexity in the patients compared to the healthy controls only during the recall of the personal pain scene. The personal stress scene was rated equally aversive but did not induce more EEG complexity. These more extensive and more readily accessible pain memories may be instrumental for the persistence of chronic pain.
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Affiliation(s)
- W Lutzenberger
- Institute of Medical Psychology and Behavioral Neurobiology, University of Tubingen, Germany
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45
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Jones AK, Derbyshire SW. Cerebral mechanisms operating in the presence and absence of inflammatory pain. Ann Rheum Dis 1996; 55:411-20. [PMID: 8774157 PMCID: PMC1010201 DOI: 10.1136/ard.55.7.411] [Citation(s) in RCA: 27] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Affiliation(s)
- A K Jones
- Human Physiology and Pain Research Laboratory, Manchester University Rheumatic Diseases Centre, Hope Hospital, Salford, United Kingdom
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46
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Porro CA, Cavazzuti M. Functional imaging studies of the pain system in man and animals. PROGRESS IN BRAIN RESEARCH 1996; 110:47-62. [PMID: 9000715 DOI: 10.1016/s0079-6123(08)62564-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Affiliation(s)
- C A Porro
- Dipartimento di Scienze Biomediche, University of Udine, Italy
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47
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Lötsch J, Mohammadian P, Hummel T, Florin S, Brune K, Geisslinger G, Kobal G. Effects of azapropazone on pain-related brain activity in human subjects. Br J Clin Pharmacol 1995; 40:545-52. [PMID: 8703660 PMCID: PMC1365209 DOI: 10.1111/j.1365-2125.1995.tb05799.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
1. The dose-related effects of azapropazone on (i) event-related and spontaneous EEG-activity and (ii) the subjects' pain ratings were investigated using an experimental human pain model based on both chemo-somatosensory event-related potentials (CSSERP) and subjects' pain ratings. 2. Healthy subjects (n = 20) participated in a placebo-controlled, randomized, double-blind, four-way cross-over study. Single doses of azapropazone (300 mg, 600 mg and 1200 mg) and placebo were administered intravenously. Each experiment consisted of five sessions (before and 1, 2, 4 and 8 h after administration of the medication). Each session lasted for approximately 40 min. In the first 20 min, pain was induced by short CO2-stimuli presented to the right nostril (phasic pain; interstimulus interval 30 s) and EEG was recorded from five positions. CSSERPs were obtained in response to painful CO2-stimuli. In the following 20 min period, tonic pain was induced by a constant stream of dry air introduced in the left nostril. Subjects rated the intensity of both phasic and tonic pain by means of a visual analogue scale. Additionally, a frequency analysis of the spontaneous EEG was performed. 3. Azapropazone reduced the pain-related CSSERP-amplitudes at frontal and parietal recording positions. This topographical pattern was observed in previous studies with opioids, while NSAIDs such as flurbiprofen and ketoprofen exerted effects at frontal and central positions. In contrast to other NSAIDs, administration of azapropazone resulted in a reduction of the frequency bands alpha 1, delta and theta of the spontaneous EEG. At the subjective level, analgesic effects of azapropazone were observed in the ratings of tonic pain. 4. Analgesic properties of azapropazone were demonstrated in man. The topographical pattern of the changes in the CSSERPs and the effects on EEG background activity suggest a central component of the analgesic action of azapropazone.
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Affiliation(s)
- J Lötsch
- Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, Germany
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49
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Lötsch J, Geisslinger G, Mohammadian P, Brune K, Kobal G. Effects of flurbiprofen enantiomers on pain-related chemo-somatosensory evoked potentials in human subjects. Br J Clin Pharmacol 1995; 40:339-46. [PMID: 8554936 PMCID: PMC1365153 DOI: 10.1111/j.1365-2125.1995.tb04556.x] [Citation(s) in RCA: 44] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023] Open
Abstract
1. The aim of the study was to investigate the analgesic effects of flurbiprofen enantiomers using an experimental pain model based on both chemo-somatosensory event-related potentials (CSSERP) and subjective pain ratings. 2. Healthy female volunteers (n = 16, age 23-36 years) participated in a placebo-controlled, randomised, double-blind, four-way crossover study. Single doses of (S)-flurbiprofen (50 mg), (R)-flurbiprofen (50 and 100 mg) and placebo were administered orally. Measurements were taken before and 2 h after administration of the medications. During each measurement, 32 painful stimuli of gaseous carbon dioxide (200 ms duration, interval approximately 30 s) of two concentrations (60 and 65% CO2 v/v) were applied to the right nostril. EEG was recorded from five positions and CSSERP were obtained in response to the painful CO2- stimuli. Additionally, subjects rated the perceived intensity of the painful stimuli by means of a visual analogue scale (VAS). 3. The CSSERP-amplitude P2, a measure of analgesic effect, decreased after administration of both (R)- and (S)-flurbiprofen, while it increased after placebo. This was statistically significant at recording positions C4 (P < 0.01) and Fz (P < 0.05). The analgesia-related decreases in evoked potential produced by (R)-flurbiprofen were dose-dependent. Comparing similar doses of (R)- and (S)-flurbiprofen, the decrease in CSSERP-amplitudes produced by the (S)-enantiomer was somewhat more pronounced, indicating a higher analgesic potency. 4. The present data indicate that both enantiomers of flurbiprofen produce analgesic effects. Since (R)-flurbiprofen caused only little toxicity in rats as compared with the (S)-enantiomer or the racemic compound, a reduction of the quantitatively most important side effects in the gastrointestinal tract might be achieved by employing (R)-flurbiprofen in pain therapy.
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Affiliation(s)
- J Lötsch
- Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, Erlangen, Germany
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Chen AC, Rappelsberger P. Brain and human pain: topographic EEG amplitude and coherence mapping. Brain Topogr 1994; 7:129-40. [PMID: 7696090 DOI: 10.1007/bf01186771] [Citation(s) in RCA: 68] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Nineteen young healthy volunteers (8 males and 11 females) participated in an experimental ice-cube cold pressor test to study topographic changes of EEG parameters in response to painful stimulation. EEG was recorded with 19 electrodes and quantified by amplitude and coherence analyses. Mean amplitudes and values for local (between adjacent electrodes) and interhemispheric (between electrodes on homologous sites of both hemispheres) coherences were computed for six frequency bands. For the evaluation of changes between EEG at rest (baseline) and EEG during painful stimulation (right or left hand), non-parametric paired Wilcoxon tests were performed. The obtained descriptive error probabilities were presented in probability maps. In the behavioural pain tolerance and subjective pain ratings, no difference in gender or stimulation condition was observed. Under painful stimulation the results showed: (A) most pronounced decrease of Alpha amplitude in the central areas and some increase of high Beta amplitude; (B) increase of local coherence for Alpha and Beta 2 mainly in central regions and centro-frontal leads; and (C) increase of interhemispheric coherence for Alpha and Beta 2 in the central areas. The results of this study indicate clearly that peripheral painful stimulation is reflected by EEG changes. Decrease of EEG amplitude and simultaneous increase of EEG coherence in the central regions can be cortical correlates of human pain.
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Affiliation(s)
- A C Chen
- Pain and Human Physiology Laboratory, University of Manchester, School of Medicine, Hope Hospital, Salforo, United Kingdom
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