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Snow NJ, Kirkland MC, Downer MB, Murphy HM, Ploughman M. Transcranial magnetic stimulation maps the neurophysiology of chronic noncancer pain: A scoping review. Medicine (Baltimore) 2022; 101:e31774. [PMID: 36401490 PMCID: PMC9678597 DOI: 10.1097/md.0000000000031774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Accepted: 10/24/2022] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND Chronic noncancer pain is a global public health challenge. It is imperative to identify biological markers ("biomarkers") to understand the mechanisms underlying chronic pain and to monitor pain over time and after interventions. Transcranial magnetic stimulation (TMS) is a promising method for this purpose. OBJECTIVES To examine differences in TMS-based outcomes between persons with chronic pain and healthy controls (HCs) and/or before versus after pain-modulating interventions and relationships between pain measures and TMS outcomes; To summarize the neurophysiological mechanisms underlying chronic pain as identified by TMS. METHODS We searched the PubMed database for literature from January 1, 1985, to June 9, 2020, with the keywords "pain" and "transcranial magnetic stimulation." Eligible items included original studies of adult human participants with pain lasting for ≥ 6 months. We completed a narrative synthesis of the study findings stratified by chronic pain etiology (primary pain, neuropathic pain, and secondary musculoskeletal pain). RESULTS The search yielded 1265 records. The final 12 articles included 244 patients with chronic pain (192 females, aged 35-65 years) and 169 HCs (89 females, aged 28-59 years). Abnormalities in TMS outcomes that reflect GABAergic and glutamatergic activities were associated with many of the disorders studied and were distinct for each pain etiology. Chronic primary pain is characterized by reduced intracortical inhibition and corticospinal excitability, chronic neuropathic pain shows evidence of increased excitation and disinhibition, and chronic secondary musculoskeletal pain involves low corticospinal excitability. DISCUSSION TMS could be a useful tool for delineating the neurophysiological underpinnings of chronic pain syndromes.
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Affiliation(s)
- Nicholas Jacob Snow
- Recovery and Performance Laboratory, Faculty of Medicine, Memorial University of Newfoundland & Labrador, St. John’s, NL, Canada
| | - Megan Christine Kirkland
- Recovery and Performance Laboratory, Faculty of Medicine, Memorial University of Newfoundland & Labrador, St. John’s, NL, Canada
| | - Matthew Bruce Downer
- Recovery and Performance Laboratory, Faculty of Medicine, Memorial University of Newfoundland & Labrador, St. John’s, NL, Canada
| | - Hannah Margaret Murphy
- Recovery and Performance Laboratory, Faculty of Medicine, Memorial University of Newfoundland & Labrador, St. John’s, NL, Canada
| | - Michelle Ploughman
- Recovery and Performance Laboratory, Faculty of Medicine, Memorial University of Newfoundland & Labrador, St. John’s, NL, Canada
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Hoelz AG, Bernardes D, Cartarozzi LP, de Oliveira ALR. Gliosis attenuation in experimental autoimmune encephalomyelitis by a combination of dimethyl fumarate and pregabalin. Front Cell Neurosci 2022; 16:921916. [PMID: 36052340 PMCID: PMC9426298 DOI: 10.3389/fncel.2022.921916] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Accepted: 07/18/2022] [Indexed: 11/16/2022] Open
Abstract
Dysregulated microglia and astrocytes have been associated with progressive neurodegeneration in multiple sclerosis (MS), highlighting the need for strategies that additionally target intrinsic inflammation in the central nervous system (CNS). The objective of the present study was to investigate the glial response in experimental autoimmune encephalomyelitis (EAE)-induced mice treated with a combination of dimethyl fumarate (DMF) and pregabalin (PGB). For that, 28 C57BL/6J mice were randomly assigned to the five experimental groups: naïve, EAE, EAE-DMF, EAE-PGB, and EAE-DMF + PGB. Pharmacological treatments were initiated with the beginning of clinical signs, and all animals were euthanized at 28 dpi for the lumbar spinal cord evaluation. The results demonstrated a stronger attenuation of the clinical presentation by the combined approach. DMF alone promoted the downregulation of Iba-1 (microglia/macrophages marker) in the ventral horn compared with the non-treated EAE animals (P < 0.05). PGB treatment was associated with reduced Iba-1 immunofluorescence in both the dorsal (P < 0.05) and ventral horn (P < 0.05) compared to EAE vehicle-treated counterparts. However, the combined approach reduced the Iba-1 marker in the dorsal (P < 0.05) and ventral (P < 0.01) horns compared to non-treated EAE animals and further reduced Iba-1 in the ventral horn compared to each drug-alone approach (P < 0.05). In addition, the combination of DMF and PGB reduced activated astrocytes (GFAP) in both the dorsal and ventral horns of the spinal cord to a naïve-like level and upregulated Nrf-2 expression. Taken together, the data herein suggest robust attenuation of the glial response in EAE mice treated with DMF and PGB.
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Central Neuropathic Pain Syndromes: Current and Emerging Pharmacological Strategies. CNS Drugs 2022; 36:483-516. [PMID: 35513603 DOI: 10.1007/s40263-022-00914-4] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/10/2022] [Indexed: 12/31/2022]
Abstract
Central neuropathic pain is caused by a disease or lesion of the brain or spinal cord. It is difficult to predict which patients will develop central pain syndromes after a central nervous system injury, but depending on the etiology, lifetime prevalence may be greater than 50%. The resulting pain is often highly distressing and difficult to treat, with no specific treatment guidelines currently available. This narrative review discusses mechanisms contributing to central neuropathic pain, and focuses on pharmacological approaches for managing common central neuropathic pain conditions such as central post-stroke pain, spinal cord injury-related pain, and multiple sclerosis-related neuropathic pain. Tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and gabapentinoids have some evidence for efficacy in central neuropathic pain. Medications from other pharmacologic classes may also provide pain relief, but current evidence is limited. Certain non-pharmacologic approaches, neuromodulation in particular, may be helpful in refractory cases. Emerging data suggest that modulating the primary afferent input may open new horizons for the treatment of central neuropathic pain. For most patients, effective treatment will likely require a multimodal therapy approach.
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Spirin NN, Kiselev DV, Karpova MS. [Neuropathic pain syndromes in patients with multiple sclerosis]. Zh Nevrol Psikhiatr Im S S Korsakova 2021; 121:22-30. [PMID: 34387442 DOI: 10.17116/jnevro202112107222] [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: 01/16/2023]
Abstract
Among the numerous pain syndromes (PS) of various localizations and types, observed in patients with multiple sclerosis (MS), the greatest attention of researchers is attracted by neuropathic PS. Neuropathic PS are often present already in the early stage of MS, significantly reduce the quality of life, hinder the social adaptation of patients, poorly respond to therapy. Central neuropathic PS, which pathogenesis is closely related with plaques in the central nervous system, are most common in patients with MS. Diagnostics of neuropathic PS in MS is based mainly on typical clinical symptoms; MRI and neurophysiological methods data are of secondary importance. This review focuses on modern concepts of three main neuropathic PS in MS: ongoing extremity pain, trigeminal neuralgia and Lhermitte's sign. Clinical symptoms of neuropathic PS, current ideas about their pathogenetic mechanisms, MRI and neurophysiological techniques data and the existing approaches to conservative therapy and surgical treatment based on randomized trials data are presented.
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Affiliation(s)
- N N Spirin
- Yaroslavl State Medical University, Yaroslavl, Russia
| | - D V Kiselev
- Yaroslavl State Medical University, Yaroslavl, Russia
| | - M S Karpova
- Yaroslavl State Medical University, Yaroslavl, Russia
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5
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Abstract
Pain is a major matter for patients with multiple sclerosis; treatment response is frequently inadequate, with a significant impact on quality of life. The estimated prevalence of pain in multiple sclerosis ranges widely (26-86%), and different subtypes of pain, mediated by specific pathophysiological mechanisms, are described. The aim of this narrative review, performed using a systematic search methodology, was to provide current, evidence-based, knowledge about the pharmacological treatment of the different kinds of pain in multiple sclerosis. We searched for relevant papers within PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and the Clinical Trials database (ClinicalTrials.gov), considering publications up to November 2019. Two authors independently selected studies for inclusion, data extraction, and bias assessment. A total of 27 randomized controlled trials were identified, but in only a few cases, patients with different pain qualities were stratified. Following a mechanism-based approach, treatment of paroxysmal pain and painful tonic spasms should be based on sodium-channel blockers, whereas treatment of ongoing extremity pain should be based on gabapentinoids and antidepressants.
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Chisari CG, Sgarlata E, Arena S, D’Amico E, Toscano S, Patti F. An update on the pharmacological management of pain in patients with multiple sclerosis. Expert Opin Pharmacother 2020; 21:2249-2263. [DOI: 10.1080/14656566.2020.1757649] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Affiliation(s)
- Clara G. Chisari
- Department “GF Ingrassia”, Section of Neurosciences, University of Catania, Catania, Italy
| | - Eleonora Sgarlata
- Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy
- Stroke Unit, Department of Medicine, Umberto I Hospital, Siracusa, Italy
| | - Sebastiano Arena
- Department “GF Ingrassia”, Section of Neurosciences, University of Catania, Catania, Italy
| | - Emanuele D’Amico
- Department “GF Ingrassia”, Section of Neurosciences, University of Catania, Catania, Italy
| | - Simona Toscano
- Department “GF Ingrassia”, Section of Neurosciences, University of Catania, Catania, Italy
| | - Francesco Patti
- Department “GF Ingrassia”, Section of Neurosciences, University of Catania, Catania, Italy
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Di Stefano G, Maarbjerg S, Truini A. Trigeminal neuralgia secondary to multiple sclerosis: from the clinical picture to the treatment options. J Headache Pain 2019; 20:20. [PMID: 30782116 PMCID: PMC6734488 DOI: 10.1186/s10194-019-0969-0] [Citation(s) in RCA: 82] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Accepted: 02/06/2019] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Trigeminal neuralgia is one of the most characteristic and difficult to treat neuropathic pain conditions in patients with multiple sclerosis. The present narrative review addresses the current evidence on diagnostic tests and treatment of trigeminal neuralgia secondary to multiple sclerosis. METHODS We searched for relevant papers within PubMed, EMBASE and the Cochrane Database of Systematic Reviews, taking into account publications up to December 2018. RESULTS Trigeminal neuralgia secondary to multiple sclerosis manifests with facial paroxysmal pain triggered by typical manoeuvres; neurophysiological investigations and MRI support the diagnosis, providing the definite evidence of trigeminal pathway damage. A dedicated MRI is required to identify pontine demyelinating plaques. In many patients with multiple sclerosis, neuroimaging and surgical evidence suggests that neurovascular compression might act in concert with the pontine plaque through a double-crush mechanism. Although no placebo-controlled trials have been conducted in these patients, according to expert opinion the first-line therapy for trigeminal neuralgia secondary to multiple sclerosis relies on sodium-channel blockers, i.e. carbamazepine and oxcarbazepine. The sedative and motor side effects of these drugs frequently warrant an early consideration for neurosurgery. Surgical procedures include Gasserian ganglion percutaneous techniques, gamma knife radiosurgery and microvascular decompression in the posterior fossa. CONCLUSIONS The relatively poor tolerability of the centrally-acting drugs carbamazepine and oxcarbazepine highlights the need to develop new selective and better-tolerated sodium-channel blockers. Prospective studies based on more advanced neuroimaging techniques should focus on how trigeminal anatomical abnormalities may be able to predict the efficacy of microvascular decompression.
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Affiliation(s)
- Giulia Di Stefano
- Department of Human Neurosciences, Sapienza University, Viale Università 30, 00185 Rome, Italy
| | - Stine Maarbjerg
- Danish Headache Center, Department of Neurology, Rigshospitalet - Glostrup, University of Copenhagen, Copenhagen, Denmark
| | - Andrea Truini
- Department of Human Neurosciences, Sapienza University, Viale Università 30, 00185 Rome, Italy
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Di Stefano G, Truini A, Cruccu G. Current and Innovative Pharmacological Options to Treat Typical and Atypical Trigeminal Neuralgia. Drugs 2018; 78:1433-1442. [PMID: 30178160 PMCID: PMC6182468 DOI: 10.1007/s40265-018-0964-9] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Trigeminal neuralgia is a representative neuropathic facial pain condition, characterised by unilateral paroxysmal pain in the distribution territory of one or more divisions of the trigeminal nerve, triggered by innocuous stimuli. A subgroup of patients with trigeminal neuralgia [TN (previously defined as atypical TN)] also suffer from concomitant continuous pain, i.e. a background pain between the paroxysmal attacks. The aim of this review is to provide current, evidence-based, knowledge about the pharmacological treatment of typical and atypical TN, with a specific focus on drugs in development. We searched for relevant papers within PubMed, EMBASE, the Cochrane Database of Systematic Reviews and the Clinical Trials database (ClinicalTrials.gov), taking into account publications up to February 2018. Two authors independently selected studies for inclusions, data extraction, and bias assessment. Carbamazepine and oxcarbazepine are the first-choice drugs for paroxysmal pain. When sodium channel blockers cannot reach full dosage because of side effects, an add-on treatment with lamotrigine or baclofen should be considered. In patients with atypical TN, both gabapentin and antidepressants are expected to be efficacious and should be tried as an add-on to oxcarbazepine or carbamazepine. Although carbamazepine and oxcarbazepine are effective in virtually the totality of patients, they are responsible for side effects causing withdrawal from treatment in an important percentage of cases. A new, better tolerated, Nav1.7 selective state-dependent, sodium channel blocker (vixotrigine) is under development. Future trials testing the effect of combination therapy in patients with TN are needed, especially in patients with concomitant continuous pain and in TN secondary to multiple sclerosis.
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Affiliation(s)
- G Di Stefano
- Department of Human Neuroscience, Sapienza University, viale Università 30, 00185, Rome, Italy
| | - A Truini
- Department of Human Neuroscience, Sapienza University, viale Università 30, 00185, Rome, Italy
| | - G Cruccu
- Department of Human Neuroscience, Sapienza University, viale Università 30, 00185, Rome, Italy.
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Solaro CM, Ferriero G. Refactory Trigeminal Neuralgia successfully treated by combination therapy (Pregabalin plus Lamotrigine). Mult Scler Relat Disord 2018; 25:165-166. [PMID: 30081317 DOI: 10.1016/j.msard.2018.07.027] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Revised: 07/13/2018] [Accepted: 07/13/2018] [Indexed: 11/30/2022]
Abstract
In MS patients (PwMS), paroxysmal symptoms (PS) are frequently reported and are often the cause of suffering. PS include Trigeminal Neuralgia (TN) that is the most widely recognized neurophatic pain syndrome. TN treatment primarily consists of antiepileptic medications such as Carbamazepine (CBZ) and Lamotrigine (LTG). CBZ is reported to be not well tolerated by PwMS for its side effects that mimic an MS exacerbation. Pregabalin (PGB) was successfully used in treating paroxysmal symptoms in PwMS. We performed a prospective open-label pilot study of PGB in combination with LTG in a group of MS patients with TN to evaluate the efficacy and tolerability of the two medications in subjects who were no-responsive or intolerant to conventional treatment. The combination of PGB and LTG may prove effective in the treatment of TN in PwMS, at small dosages, along with the possibility of minimizing adverse effects, while significantly improving pain control.
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Affiliation(s)
| | - Giorgio Ferriero
- Unit of Rehabilitation and Functional Recovery, IRCCS Istituti Clinici Scientifici Maugeri, Lissone (MB), Italy.
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Abstract
INTRODUCTION Unique among the different neuropathic pain conditions, trigeminal neuralgia frequently has an excellent response to some selected drugs, which, on the other hand, often entail disabling side effects. Physicians should be therefore acquainted with the management of these drugs and the few alternative options. Areas covered: This article, based on a systematic literature review, describes the pharmacological options, and indicates the future perspectives for treating trigeminal neuralgia. The article therefore provides current, evidence-based knowledge about the pharmacological treatment of trigeminal neuralgia, and suggests a practical approach to the various drugs, including starting dose, titration and side effects. Expert commentary: Carbamazepine and oxcarbazepine are the reference standard drugs for treating patients with trigeminal neuralgia. They are effective in most patients. The undesired effects however cause withdrawal from treatment or a dosage reduction to an insufficient level in many patients. Sodium channel blockers selective for the sodium channel 1.7 (Nav1.7) receptor, currently under development, might be an alternative, better-tolerated pharmacological option in the next future.
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Affiliation(s)
- Giulia Di Stefano
- a Department of Neurology and Psychiatry , University Sapienza , Roma , Italy
| | - Andrea Truini
- a Department of Neurology and Psychiatry , University Sapienza , Roma , Italy
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Turcotte DA, Doupe M, Torabi M, Gomori AJ, Ethans K, Esfahani F, Galloway K, Namaka MP. Paroxetine vs pregabalin for the management of neuropathic pain in multiple sclerosis. World J Anesthesiol 2014; 3:181-188. [DOI: 10.5313/wja.v3.i2.181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2013] [Revised: 06/06/2014] [Accepted: 06/16/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To compare the effectiveness and tolerability of paroxetine vs pregabalin for the management of multiple sclerosis (MS)-induced neuropathic pain (NPP).
METHODS: A randomized, flexible-dose open-label 8-wk study involving 21 relapsing-remitting MS patients with MS-induced NPP was conducted to evaluate the effectiveness and tolerability of pregabalin versus paroxetine for pain management. The trial included a 3-wk dose titration phase followed by a 5-wk stable dose phase. Primary outcome measures included daily patient-reported pain intensity as measured using a 100 mm visual analogue scale (VASpain) and daily impact of pain on daily activities (VASimpact). Hierarchical regression modeling was conducted on each outcome to determine if within person VAS trajectory for pain and impact differed across study groups, during 56 d follow-up.
RESULTS: Attrition rates were significantly greater (P < 0.001) in the paroxetine versus pregabalin study group (70% vs 18.2%, respectively). Average study duration between study groups also significantly differed (P < 0.001). Paroxetine participants completed an average of 27.3 d of treatment vs 49.5 d in the pregabalin group, with the majority of patients withdrawing due to adverse events. Due to the high attrition rates in the paroxetine study arm, the investigators stopped the study prior to achieving complete recruitment. As such, no significant differences between pregabalin and paroxetine study arms were noted for the primary outcome measures (VASpain, VASimpact). Comparative assessment of baseline patient characteristics also revealed no significant differences between the study arms.
CONCLUSION: High attrition rates associated with paroxetine use suggest that it be used with caution for MS-induced NPP. Efficacy outcomes could not be assessed due to attrition.
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Khan N, Smith MT. Multiple sclerosis-induced neuropathic pain: pharmacological management and pathophysiological insights from rodent EAE models. Inflammopharmacology 2014; 22:1-22. [PMID: 24234347 PMCID: PMC3933737 DOI: 10.1007/s10787-013-0195-3] [Citation(s) in RCA: 79] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2013] [Accepted: 10/22/2013] [Indexed: 01/05/2023]
Abstract
In patients with multiple sclerosis (MS), pain is a frequent and disabling symptom. The prevalence is in the range 29-86 % depending upon the assessment protocols utilised and the definition of pain applied. Neuropathic pain that develops secondary to demyelination, neuroinflammation and axonal damage in the central nervous system is the most distressing and difficult type of pain to treat. Although dysaesthetic extremity pain, L'hermitte's sign and trigeminal neuralgia are the most common neuropathic pain conditions reported by patients with MS, research directed at gaining insight into the complex mechanisms underpinning the pathobiology of MS-associated neuropathic pain is in its relative infancy. By contrast, there is a wealth of knowledge on the neurobiology of neuropathic pain induced by peripheral nerve injury. To date, the majority of research in the MS field has used rodent models of experimental autoimmune encephalomyelitis (EAE) as these models have many clinical and neuropathological features in common with those observed in patients with MS. However, it is only relatively recently that EAE-rodents have been utilised to investigate the mechanisms contributing to the development and maintenance of MS-associated central neuropathic pain. Importantly, EAE-rodent models exhibit pro-nociceptive behaviours predominantly in the lower extremities (tail and hindlimbs) as seen clinically in patients with MS-neuropathic pain. Herein, we review research to date on the pathophysiological mechanisms underpinning MS-associated neuropathic pain as well as the pharmacological management of this condition. We also identify knowledge gaps to guide future research in this important field.
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Affiliation(s)
- Nemat Khan
- Centre for Integrated Preclinical Drug Development and School of Pharmacy, The University of Queensland, Level 3, Steele Building, St. Lucia Campus, Brisbane, QLD 4072 Australia
| | - Maree T. Smith
- Centre for Integrated Preclinical Drug Development and School of Pharmacy, The University of Queensland, Level 3, Steele Building, St. Lucia Campus, Brisbane, QLD 4072 Australia
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13
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Jawahar R, Oh U, Yang S, Lapane KL. A Systematic Review of Pharmacological Pain Management in Multiple Sclerosis. Drugs 2013; 73:1711-22. [DOI: 10.1007/s40265-013-0125-0] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Khan F, Amatya B, Turner-Stokes L. Symptomatic therapy and rehabilitation in primary progressive multiple sclerosis. Neurol Res Int 2011; 2011:740505. [PMID: 22013521 PMCID: PMC3196037 DOI: 10.1155/2011/740505] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2011] [Accepted: 07/13/2011] [Indexed: 11/26/2022] Open
Abstract
Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system and a major cause of chronic neurological disability in young adults. Primary progressive MS (PPMS) constitutes about 10% of cases, and is characterized by a steady decline in function with no acute attacks. The rate of deterioration from disease onset is more rapid than relapsing remitting and secondary progressive MS types. Multiple system involvement at onset and rapid early progression have a worse prognosis. PPMS can cause significant disability and impact on quality of life. Recent studies are biased in favour of relapsing remitting patients as treatment is now available for them and they are more likely to be seen at MS clinics. Since prognosis for PPMS is worse than other types of MS, the focus of rehabilitation is on managing disability and enhancing participation, and application of a "neuropalliative" approach as the disease progresses. This chapter presents the symptomatic treatment and rehabilitation for persons with MS, including PPMS. A multidisciplinary approach optimizes the intermediate and long-term medical, psychological and social outcomes in this population. Restoration and maintenance of functional independence and societal reintegration, and issues relating to quality of life are addressed in rehabilitation processes.
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Affiliation(s)
- Fary Khan
- Department of Medicine, Dentistry and Health Sciences at The University of Melbourne, Royal Melbourne Hospital and Western Health, Rehabilitation Service—Royal Melbourne Hospital, Poplar Road, Parkville, Melbourne, VIC 3052, Australia
| | - Bhasker Amatya
- Department of Rehabilitation Medicine, Royal Melbourne Hospital, 34-54 Poplar Road Parkville, Melbourne, VIC 3052, Australia
| | - Lynne Turner-Stokes
- Regional Rehabilitation Unit, Northwick Park Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, UK
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Abstract
Although extracts from the cannabis plant have been used medicinally for thousands of years, it is only within the last 2 decades that our understanding of cannabinoid physiology and the provision of evidence for therapeutic benefit of cannabinoids has begun to accumulate. This review provides a background to advances in our understanding of cannabinoid receptors and the endocannabinoid system, and then considers how cannabinoids may help in the management of multiple sclerosis (MS). The relative paucity of treatments for MS-related symptoms has led to experimentation by patients with MS in a number of areas including the use of cannabis extracts. An increasing amount of evidence is now emerging to confirm anecdotal reports of symptomatic improvement, particularly for muscle stiffness and spasms, neuropathic pain and sleep and bladder disturbance, in patients with MS treated with cannabinoids. Trials evaluating a role in treating other symptoms such as tremor and nystagmus have not demonstrated any beneficial effects of cannabinoids. Safety profiles of cannabinoids seem acceptable, although a slow prolonged period of titration improves tolerability. No serious safety concerns have emerged. Methodological issues in trial design and treatment delivery are now being addressed. In addition, recent experimental evidence is beginning to suggest an effect of cannabinoids on more fundamental processes important in MS, with evidence of anti-inflammation, encouragement of remyelination and neuroprotection. Trials are currently under way to test whether cannabinoids may have a longer term role in reducing disability and progression in MS, in addition to symptom amelioration, where indications are being established.
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Affiliation(s)
- John P Zajicek
- Clinical Neurology Research Group, Peninsula College of Medicine and Dentistry, Plymouth, UK.
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Bagnato F, Centonze D, Galgani S, Grasso MG, Haggiag S, Strano S. Painful and involuntary multiple sclerosis. Expert Opin Pharmacother 2011; 12:763-77. [PMID: 21323633 DOI: 10.1517/14656566.2011.540239] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
INTRODUCTION Pain, dysphagia, respiratory problems, sexual and cardiovascular dysfunctions may occur in patients with MS. AREAS COVERED In the present review, we attempt to summarize the current knowledge on the impact pain, dysphagia, respiratory problems, sexual and cardiovascular dysfunctions have in patients with MS. EXPERT OPINION To effectively manage MS, it is essential that these symptoms are recognized as early as possible and treated by a rehabilitative multidisciplinary approach, based on proven scientific evidence.
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Affiliation(s)
- Francesca Bagnato
- Vanderbilt University Institute of Imaging Science 1161 21st Ave. S. AA1105 MCN Radiology Department, Nashville, TN 37232, USA.
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Abstract
Multiple sclerosis (MS) is an inflammatory, demyelinating, autoimmune disease of the CNS. There are currently a number of disease-modifying medications for MS that modulate or suppress the immune system; however, these medications do not directly relieve MS symptoms, which include visual deficits, gait problems, sensory deficits, weakness, tremor, spasticity and pain, among others. Pain is a common symptom in MS which has recently been estimated to be experienced by more than 40% of patients. Nociceptive pain occurs as an appropriate physiological response transmitted to a conscious level when nociceptors in bone, muscle or any body tissue are activated, warning the organism of tissue damage. Neuropathic pain is initiated as a direct consequence of a lesion or disease affecting the somatosensory system, with no physiological advantage. Nociceptive and neuropathic pain in MS may be present concurrently and at different stages of the disease, and may be associated with other symptoms. Central neuropathic pain has been reported to be among the most common pain syndromes in MS. It is described as constant, often spontaneous, burning occurring more frequently in the lower limbs. Treatment typically includes tricyclic antidepressants and antiepileptic medications, although studies have been conducted in relatively small samples and optimal dosing has not been confirmed. Cannabinoids have been among the few treatments studied in well designed, randomized, placebo-controlled trials for central neuropathic pain. In the largest of these trials, which included 630 subjects, a 15-week comparison between Delta9-tetrahydrocannabinol and placebo was performed. More patients receiving active treatment perceived an improvement in pain than those receiving placebo, although approximately 20% of subjects reported worsening of pain while on active treatment. Trigeminal neuralgia, while affecting less than 5% of patients with MS, is the most studied pain syndrome. The pain can be extreme and is typically treated with carbamazepine, although adverse effects can mimic an MS exacerbation. Painful topic spasms occur in approximately 11% of the MS population and are treated with antispasticity medications such as baclofen and benzodiazepines. Gabapentin has also demonstrated efficacy, but all studies have included small sample sizes. In general, evidence for treating pain in MS is limited. Many clinical features of pain are often unrecognized by clinicians and are difficult for patients to describe. Treatment is often based on anecdotal reports and clinical experience. We present a review of treatment options for pain in MS, which should serve to update current knowledge, highlight shortcomings in clinical research and provide indications towards achieving evidence-based treatment of pain in MS.
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