Chronic Pain In Multiple Sclerosis Research Articles

Coupling cognitive and brainstem dysfunction in multiple sclerosis-related chronic neuropathic limb pain.

Chronic pain in multiple sclerosis is common and difficult to treat. Its mechanisms remain incompletely understood. Dysfunction of the descending pain modulatory system is known to contribute to human chronic pain conditions. However, it is not clear how alterations in executive function influence this network, despite healthy volunteer studies linking function of the descending pain modulatory system, to cognition. In adults with multiple sclerosis-associated chronic neuropathic limb pain, compared to those without pain, we hypothesized altered functional connectivity of the descending pain modulatory system, coupled to executive dysfunction. Specifically we hypothesized reduced mental flexibility, because of potential importance in stimulus reappraisal. To investigate these hypotheses, we conducted a case-control cross-sectional study of 47 adults with relapsing remitting multiple sclerosis (31 with chronic neuropathic limb pain, 16 without pain), employing clinical, neuropsychological, structural, and functional MRI measures. We measured brain lesions and atrophy affecting descending pain modulatory system structures. Both cognitive and affective dysfunctions were confirmed in the chronic neuropathic limb pain group, including reduced mental flexibility (Delis Kaplan Executive Function System card sorting tests P < 0.001). Functional connectivity of rostral anterior cingulate and ventrolateral periaqueductal gray, key structures of the descending pain modulatory system, was significantly lower in the group experiencing chronic neuropathic pain. There was no significant between-group difference in whole-brain grey matter or lesion volumes, nor lesion volume affecting white matter tracts between rostral anterior cingulate and periaqueductal gray. Brainstem-specific lesion volume was higher in the chronic neuropathic limb pain group (P = 0.0017). Differential functional connectivity remained after correction for brainstem-specific lesion volume. Gabapentinoid medications were more frequently used in the chronic pain group. We describe executive dysfunction in people with multiple sclerosis affected by chronic neuropathic pain, along with functional and structural MRI evidence compatible with dysfunction of the descending pain modulatory system. These findings extend understanding of close inter-relationships between cognition, function of the descending pain modulatory system, and chronic pain, both in multiple sclerosis and more generally in human chronic pain conditions. These findings could support application of pharmacological and cognitive interventions in chronic neuropathic pain associated with multiple sclerosis.

Virtual Reality as an Intervention for Chronic Pain in Multiple Sclerosis (4626)

Virtual Reality as an Intervention for Chronic Pain in Multiple Sclerosis (4626)

A voxel-based lesion symptom mapping analysis of chronic pain in multiple sclerosis.

Pain is one of the most disabling symptoms in multiple sclerosis. Chronic pain in multiple sclerosis is often neuropathic in nature, although a clear-cut distinction with nociceptive pain is not easy. The aim of our study was to analyze the MRIs of multiple sclerosis patients with chronic pain in order to explore possible associations with lesion sites, on a voxel-by-voxel basis. We enrolled patients aged > 18 years with multiple sclerosis in accordance with the 2010 McDonald criteria. Patients meeting criteria for persistent pain (frequent or constant pain lasting > 3 months) were included in the "pain group". The other patients were included in the "no pain group". We outlined lesions on FLAIR MRI scans using a semi-automated edge finding tool. To detect the association between lesion localization and persistent pain, images were analysed with the voxel-based lesion symptom mapping methods implemented in the (nonparametric mapping software included into the MRIcron. We enrolled 208 MS patients (140 F, mean age 55.2 ± 9.4 years; 176 RR, 28 progressive MS; mean EDSS 2.0 + 2.0). Pain group included 96 patients and no pain group 112 patients. Lesions of the right dorsolateral prefrontal area were significantly more prevalent in patients without pain, whereas periventricular posterior lesions were significantly more prevalent in patients with persistent pain. Our data suggest a role of the right dorsolateral prefrontal cortex in the modulation of pain perception and in the occurrence of chronic pain in MS patients. Our data also support a hemispheric asymmetry in pain perception and modulation.

Long-term assessment of the cognitive effects of nabiximols in patients with multiple sclerosis: A pilot study

ObjectiveModerate to severe spasticity is commonly reported in Multiple Sclerosis (MS) and its management is still a challenge. Cannabinoids were recently suggested as add-on therapy for the treatment of spasticity and chronic pain in MS but there is no conclusive scientific evidence on their safety, especially on cognition and over long periods. The aim of this prospective pilot study was to assess the long-term effects of a tetrahydrocannabinol-cannabidiol (THC/CBD) oromucosal spray (Sativex®) on cognition, mood and anxiety. Patients and MethodsAn extensive and specific battery of neuropsychological tests (Symbol Digit Modalities Test-SDMT, California Verbal Learning Test-CVLT, Brief Visuospatial Memory Test-BVMT; PASAT-3 and 2; Free and Cued Selective Remind Test-FCSRT, Index of Sensitivity of Cueing-ISC) was applied to longitudinally investigate different domains of cognition in 20 consecutive MS patients receiving Sativex for spasticity. The primary endpoint was to assess any variation in cognitive performance. Secondary outcomes regarding mood and anxiety were investigated by means of Beck Depression Inventory (BDI) and Hamilton Anxiety Rating Scale (HAM-A). Any change in patients’ spasticity was evaluated using the 0–10 Numerical Rating Scale (NRS). ResultsTwenty per protocol patients were followed up and evaluated at baseline, 6 and 12 months. Domains involving processing speed and auditory verbal memory significantly improved within the first 6 months of therapy (SDMT: p < 0.001; CVLT: p = 0.0001). Mood and anxiety did not show any significant variation. Additionally, the NRS score significantly improved since the beginning (p < 0.0001). ConclusionsThese results are encouraging in supporting possible long-term benefits of Sativex on cognition and a wider role than symptom alleviator. Further studies on larger groups of patients would be necessary in order to test this intriguing possibility.

Cross-network coupling of neural oscillations in the dynamic pain connectome reflects chronic neuropathic pain in multiple sclerosis.

Sensory perceptions are coded by complex neural dynamics of regional communication in the brain. Thus, sensory abnormalities such as chronic pain may occur when neural dynamics go awry. Previous studies of cross-network dynamic functional connectivity in chronic pain identified abnormalities but were based on functional MRI which only captures slow temporal features. Here we conducted a magnetoencephalography (MEG) study to investigate fine temporal dynamics of aberrant cross-regional and cross-network communication of the dynamic pain connectome in patients with chronic pain. We also introduced a novel measure, dynamic functional coupling, to quantify the variability of brain communication. The study was performed in 33 people who had chronic pain associated with multiple sclerosis and 30 healthy controls. We found that patients with chronic pain exhibited abnormalities in cross-network functional coupling across multiple frequency bands (theta, alpha, beta, gamma), between the salience network and 3 other networks: the ascending nociceptive pathway, descending anti-nociceptive pathway, and the default mode network. However, these cross-network abnormalities involved different frequency bands in patients with neuropathic versus non-neuropathic chronic pain. Furthermore, cross-network abnormalities were linked to pain severity and pain interference. Our findings implicate broadband cross-network abnormalities as hallmark features of chronic pain in multiple sclerosis.

Mindfulness-based cognitive therapy and cognitive behavioral therapy for chronic pain in multiple sclerosis: a randomized controlled trial protocol

BackgroundChronic pain is one of the most prevalent and disabling symptoms associated with multiple sclerosis (MS). Individuals with MS are interested in nonpharmacologic pain management approaches. Cognitive-behavioral therapy (CBT) is efficacious in improving MS-related pain outcomes. Mindfulness-based cognitive therapy (MBCT) is a promising, alternative approach. Little is known about moderators of these treatments’ outcomes, however. This article describes the study protocol for the first randomized controlled trial comparing MBCT, CBT, and usual care and examining treatment effect moderators in individuals with chronic pain and MS.MethodsWe will conduct a single-center, randomized, single blind, parallel-group trial comparing MBCT, CBT, and usual care in adults with MS and chronic pain. Both interventions will be delivered via eight group sessions using videoconferencing technology. Primary (average pain intensity) and secondary outcomes (including pain interference, depressive symptoms, fatigue, and sleep) will be assessed pre-treatment, mid-treatment, post-treatment, and at 6-month follow up. Potential treatment moderators will be assessed pre-treatment. We hypothesize that participants randomly assigned to MBCT or CBT will report significantly greater reductions in average pain intensity than participants assigned to usual care at post-treatment (primary study endpoint) and 6-month follow up. We also hypothesize that mindfulness, pain catastrophizing, and behavioral activation pre-treatment will moderate response to both active treatments, but not response to usual care.DiscussionFindings will provide important new information about the efficacy and moderators of two nonpharmacologic pain management approaches delivered using technology to overcome common barriers to treatment access. The knowledge gained may lead to better patient-treatment matching and, ultimately, better pain treatment outcomes in MS.Trial registrationClinicalTrials.gov, NCT03782246. Registered on 20 December 2018.

Do non-pharmacological interventions improve chronic pain in multiple sclerosis? - A Cochrane Review summary with commentary.

The aim of this commentary is to discuss the rehabilitation perspective in the recently published Cochrane Review "Non-pharmacological interventions for chronic pain in multiple sclerosis" by Amatya, Young & Khan.1, under the direct supervision of Multiple Sclerosis and Rare Diseases of the CNS group. This Cochrane Corner is produced in agreement with NeuroRehabilitation by Cochrane Rehabilitation.

Advances in the Understanding and Management of Chronic Pain in Multiple Sclerosis: a Comprehensive Review.

Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system that can lead to severe physical, cognitive, and neurological deficits that often manifest in young adults. Central neuropathic pain is a common presenting symptom, often prompting patients to seek treatment with opioids, NSAIDS, antiepileptics, and antidepressants despite minimal effectiveness and alarming side-effect profiles. Additionally, spasticity occurs in more than 80% of MS patients and is an important consideration for further study in treatment. Related to inconsistencies in pain presentation and clinical reporting, current studies continue to investigate clinical patient presentation to define chronic pain characteristics to optimize treatment plans. Although often neuropathic in origin, the complex nature of such pain necessitates a multimodal approach for adequate treatment. While psychiatric comorbidities typically remain unchanged in their severity over time, physical conditions may lead to worsening chronic pain long-term, often due to decreased quality of life. The prevalence of neuropathic pain is ~ 86% in patients with multiple sclerosis and most commonly presents as extremity pain, trigeminal neuralgia, back pain, or headaches. As MS symptoms are frequently unremitting and poorly responsive to conventional medical management, recent attention has been given to novel interventions for management of pain. Among these, medicinal cannabis therapy, targeted physical therapy, and neuromodulation offer promising results. In this review, we provide a comprehensive update of the current perspective of MS pathophysiology, symptomatology, and treatment.

Non-pharmacological interventions for chronic pain in multiple sclerosis.

Chronic pain is common and significantly impacts on the lives of persons with multiple sclerosis (pwMS). Various types of non-pharmacological interventions are widely used, both in hospital and ambulatory/mobility settings to improve pain control in pwMS, but the effectiveness and safety of many non-pharmacological modalities is still unknown. This review aimed to investigate the effectiveness and safety of non-pharmacological therapies for the management of chronic pain in pwMS. Specific questions to be addressed by this review include the following.Are non-pharmacological interventions (unidisciplinary and/or multidisciplinary rehabilitation) effective in reducing chronic pain in pwMS?What type of non-pharmacological interventions (unidisciplinary and/or multidisciplinary rehabilitation) are effective (least and most effective) and in what setting, in reducing chronic pain in pwMS? A literature search was performed using the specialised register of the Cochrane MS and Rare Diseases of the Central Nervous System Review Group, using the Cochrane MS Group Trials Register which contains CENTRAL, MEDLINE, Embase, CINAHL, LILACUS, Clinical trials.gov and the World Health Organization International Clinical Trials Registry Platform on 10 December 2017. Handsearching of relevant journals and screening of reference lists of relevant studies was carried out. All published randomised controlled trials (RCTs)and cross-over studies that compared non-pharmacological therapies with a control intervention for managing chronic pain in pwMS were included. Clinical controlled trials (CCTs) were eligible for inclusion. All three review authors independently selected studies, extracted data and assessed the methodological quality of the studies using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) tool for best-evidence synthesis. Pooling data for meta-analysis was not possible due to methodological, clinical and statistically heterogeneity of the included studies. Overall, 10 RCTs with 565 participants which investigated different non-pharmacological interventions for the management of chronic pain in MS fulfilled the review inclusion criteria. The non-pharmacological interventions evaluated included: transcutaneous electrical nerve stimulation (TENS), psychotherapy (telephone self-management, hypnosis and electroencephalogram (EEG) biofeedback), transcranial random noise stimulation (tRNS), transcranial direct stimulation (tDCS), hydrotherapy (Ai Chi) and reflexology.There is very low-level evidence for the use of non-pharmacological interventions for chronic pain such as TENS, Ai Chi, tDCS, tRNS, telephone-delivered self-management program, EEG biofeedback and reflexology in pain intensity in pwMS. Although there were improved changes in pain scores and secondary outcomes (such as fatigue, psychological symptoms, spasm in some interventions), these were limited by methodological biases within the studies. Despite the use of a wide range of non-pharmacological interventions for the treatment of chronic pain in pwMS, the evidence for these interventions is still limited or insufficient, or both. More studies with robust methodology and greater numbers of participants are needed to justify the effect of these interventions for the management of chronic pain in pwMS.

Non-pharmacological interventions for chronic pain in multiple sclerosis: A Cochrane systematic review

Chronic pain is common and significantly impacts on the lives of persons with multiple sclerosis (MS). Various types of non-pharmacological interventions are used to improve pain control in persons with MS (pwMS), however the effectiveness and safety of many modalities is still unknown. This review evaluated the effectiveness of currently used non-pharmacological interventions for chronic pain in pwMS. A literature search was performed using the Cochrane MS Group Trials Register which contains Cochrane CENTRAL, Medline, EMBASE, CINAHL, LILACUS, Clinical trials.gov and World Health Organisation International Clinical Trials Registry Platform in April 2017. Manual searching in the relevant journals and screening of reference lists of studies was done. Randomised controlled trials (RCTs), crossover studies and clinical controlled trials were included. All authors independently selected studies, extracted data and assessed the methodological quality. Pooling data for meta-analysis was not possible due to methodological/statistical heterogeneity of included studies. Overall, 12 RCTs (610 participants), which investigated different non-pharmacological interventions for the management of chronic pain in MS fulfilled the review inclusion criteria. The non-pharmacological interventions evaluated included: transcutaneous electrical nerve stimulation (TENS), psychotherapy (telephone self-management, hypnosis and electroencephalogram biofeedback), transcranial random noise stimulation (tRNS), transcranial direct stimulation (tDCS), hydrotherapy (Ai Chi) and reflexology. The findings suggest that there is “low level” or limited evidence for the use of evaluated non-pharmacological management for chronic pain in MS. Though, there is improved changes in pain scores and secondary outcomes, these were not clinically or statistically significant for TENS for lower back pain and tRNS, hydrotherapy exercises, tDCS, reflexology and psychotherapy for overall pain. The evidence was limited for other interventions. Despite the use of wide range of non-pharmacological interventions for the treatment of chronic pain in pwMS, the evidence for these interventions is still limited and/or insufficient. More robust studies are needed to justify the beneficial effect of these interventions.

Sensory Function and Chronic Pain in Multiple Sclerosis.

Objective To examine whether hypoesthesia and chronic pain are related in patients with MS. Methods Sixty-seven MS patients with pain and 80 persons without MS were included. Sensory functioning was tested by bedside neurological examination. Touch, joint position (dorsal column-medial lemniscus pathway), temperature sense, and pain (spinothalamic tract) were tested. Pain intensity was measured by the Colored Analogue Scale (CAS Intensity) and the Faces Pain Scale (FPS); pain affect was also measured by CAS Affect and Number of Words Chosen-Affective (NWC-A). Mood was assessed with the SCL-90 anxiety and depression subscales and the Beck Depression Inventory (BDI). Results A significant negative relationship was found between pain intensity and the function of the dorsal column-medial lemniscal pathway, but not with the spinothalamic tract. Conclusion In addition to the already known relation between hyperesthesia and pain, hypoesthesia for touch and joint position also seems to be related to chronic pain in MS patients.

CaMKIIα Mediates the Effect of IL-17 To Promote Ongoing Spontaneous and Evoked Pain in Multiple Sclerosis.

Pain is a common and severe symptom in multiple sclerosis (MS), a chronic inflammatory and demyelinating disease of the CNS. The neurobiological mechanism underlying MS pain is poorly understood. In this study, we investigated the role of Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) in driving chronic pain in MS using a mouse experimental autoimmune encephalomyelitis (EAE) model. We found that spinal CaMKIIα activity was enhanced in EAE, correlating with the development of ongoing spontaneous pain and evoked hypersensitivity to mechanical and thermal stimuli. Prophylactic or acute administration of KN93, a CaMKIIα inhibitor, significantly reduced the clinical scores of EAE and attenuated mechanical allodynia and thermal hyperalgesia in EAE. siRNA targeting CaMKIIα reversed established mechanical and thermal hypersensitivity in EAE mice. Furthermore, CaMKIIαT286A point mutation mice showed significantly reduced EAE clinical scores, an absence of evoked pain, and ongoing spontaneous pain when compared with littermate wild-type mice. We found that IL-17 is responsible for inducing but not maintaining mechanical and thermal hyperalgesia that is mediated by CaMKIIα signaling in EAE. Together, these data implicate a critical role of CaMKIIα as a cellular mechanism for pain and neuropathy in multiple sclerosis and IL-17 may act upstream of CaMKIIα in the generation of pain.SIGNIFICANCE STATEMENT Pain is highly prevalent in patients with multiple sclerosis (MS), significantly reducing patients' quality of life. Using the experimental autoimmune encephalomyelitis (EAE) model, we were able to study not only evoked hyperalgesia, but also for the first time to demonstrate spontaneous pain that is also experienced by patients. Our study identified a role of spinal CaMKIIα in promoting and maintaining persistent ongoing spontaneous pain and evoked hyperalgesia pain in EAE. We further demonstrated that IL-17 contributes to persistent pain in EAE and functions as an upstream regulator of CaMKIIα signaling. These data for the first time implicated CaMKIIα and IL-17 as critical regulators of persistent pain in EAE, which may ultimately offer new therapeutic targets for mitigating pain in multiple sclerosis.

Chronic pain in multiple sclerosis: A 10-year longitudinal study

Background and purposePain is a common symptom associated with multiple sclerosis (MS), and has lasting effects on an individual's functional capacity and quality of life. A wide range of prevalence rates of pain (between 23% and 90%)have been reported in MS and this is mainly due to the methodological differences amongst the studies such as variability in patient sources, method of sampling and the definition of pain used. Chronic pain in MS, defined as pain lasting for greater than 3–6 months, can have a significant impact on their biopsychosocial health, including negative impact on activities of daily living, relationships and social participation. The long-term course of MS-related pain and its impact in an Australian cohort over a 7-year period has been investigated earlier. The aim of this longitudinal study was to describe the impact of chronic pain, pain-related disability and carer burden in persons with MS over a 10-year period. The aim of this longitudinal study was to describe the impact of chronic pain, pain-related disability and carer burden in persons with MS over a 10-year period. MethodsThis was a prospective longitudinal study conducted at the Rehabilitation Department of Royal Melbourne Hospital (RMH), a tertiary referral hospital in Victoria and Australia. The source of participants was from the RMH MS database and contains detailed MS patient information including demographic data, diagnosis details (using McDonald's criteria), pain characteristics. Structured face-face interviews and validated measures were used, which include the visual analogue scale (VAS); chronic pain grade (CPG); the assessment of quality of life (AQoL) and the carer strain index (CSI). The mean age of the participants (n=70) was 55.3 years and majority (70%) were female. ResultsThe mean age of the participants (n=70) was 55.3 years and majority (70%) were female. The findings show that over time (10 years), participants report having greater bilateral bodily pain and greater description of pain as ‘worse as it could be’. Pain types were similar to 7-years follow-up but remained higher than baseline. There was a significant deterioration in quality of life in those with more severe CPG over time. Almost half of the participants 31 (44%) required care either from a private carer, institution or from a family member. Although fear of taking medications and side effects were common barriers to treatment for pain, there was an increase in the use of pharmacological treatment over time and an increase in the use of healthcare services, mainly neurologists and general practitioners. ConclusionsThe pain measures reported by the participants were similar to those at the 7-year follow-up except there was a greater representation of bilateral pain locations (limb, trunk and facial pain) compared to baseline and 7-year follow-up. At 10-year follow-up, more participants used medications compared to 7-year follow-up and there was an increase in the use of health professionals at the 10-year follow-up. At the 10-year follow up QoL of the participants deteriorated significantly and more participants had progressed to higher CPG III and CPG IV. This study demonstrates that chronic pain is a significant issue over time in MS, with clinical and health implications, impact on quality of life, disability and healthcare utilization. ImplicationsGreater awareness of chronic pain in pwMS, cognitive classifications and an interdisciplinary approach is required to improve long-term patient outcomes and well-being.

Non-pharmacological interventions for chronic pain in multiple sclerosis

BACKGROUND Chronic pain is common and significantly impacts on the lives of persons with multiple sclerosis (pwMS). Various types of non-pharmacological interventions are widely used, both in hospital and ambulatory/mobility settings to improve pain control in pwMS, but the effectiveness and safety of many non-pharmacological modalities is still unknown. OBJECTIVES This review aimed to investigate the effectiveness and safety of non-pharmacological therapies for the management of chronic pain in pwMS. Specific questions to be addressed by this review include the following.Are non-pharmacological interventions (unidisciplinary and/or multidisciplinary rehabilitation) effective in reducing chronic pain in pwMS?What type of non-pharmacological interventions (unidisciplinary and/or multidisciplinary rehabilitation) are effective (least and most effective) and in what setting, in reducing chronic pain in pwMS? SEARCH METHODS A literature search was performed using the specialised register of the Cochrane MS and Rare Diseases of the Central Nervous System Review Group, using the Cochrane MS Group Trials Register which contains CENTRAL, MEDLINE, Embase, CINAHL, LILACUS, Clinical trials.gov and the World Health Organization International Clinical Trials Registry Platform on 10 December 2017. Handsearching of relevant journals and screening of reference lists of relevant studies was carried out. SELECTION CRITERIA All published randomised controlled trials (RCTs)and cross-over studies that compared non-pharmacological therapies with a control intervention for managing chronic pain in pwMS were included. Clinical controlled trials (CCTs) were eligible for inclusion. DATA COLLECTION AND ANALYSIS All three review authors independently selected studies, extracted data and assessed the methodological quality of the studies using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) tool for best-evidence synthesis. Pooling data for meta-analysis was not possible due to methodological, clinical and statistically heterogeneity of the included studies. MAIN RESULTS Overall, 10 RCTs with 565 participants which investigated different non-pharmacological interventions for the management of chronic pain in MS fulfilled the review inclusion criteria. The non-pharmacological interventions evaluated included: transcutaneous electrical nerve stimulation (TENS), psychotherapy (telephone self-management, hypnosis and electroencephalogram (EEG) biofeedback), transcranial random noise stimulation (tRNS), transcranial direct stimulation (tDCS), hydrotherapy (Ai Chi) and reflexology.There is very low-level evidence for the use of non-pharmacological interventions for chronic pain such as TENS, Ai Chi, tDCS, tRNS, telephone-delivered self-management program, EEG biofeedback and reflexology in pain intensity in pwMS. Although there were improved changes in pain scores and secondary outcomes (such as fatigue, psychological symptoms, spasm in some interventions), these were limited by methodological biases within the studies. AUTHORS' CONCLUSIONS Despite the use of a wide range of non-pharmacological interventions for the treatment of chronic pain in pwMS, the evidence for these interventions is still limited or insufficient, or both. More studies with robust methodology and greater numbers of participants are needed to justify the effect of these interventions for the management of chronic pain in pwMS.

Pain affects depression through anxiety, fatigue, and sleep in multiple sclerosis.

Over a quarter million individuals in the United States have multiple sclerosis (MS). Chronic pain and depression are disproportionately high in this population. The purpose of this study was to examine the relationship between chronic pain and depression in MS and to examine potentially meditational effects of anxiety, fatigue, and sleep. We used cross-sectional data from self-reported instruments measuring multiple symptoms and quality of life indicators in this study. We used structural equation modeling to model direct and indirect effects of pain on depression in a sample of 1,245 community-dwelling individuals with MS. Pain interference, depression, fatigue, and sleep disturbance were modeled as latent variables with 2 to 3 indicators each. The model controlled for age, sex, disability status (Expanded Disability Status Scale), and social support. A model with indirect effects of pain on depression had adequate fit and accounted for nearly 80% of the variance in depression. The effects of chronic pain on depression were almost completely mediated by fatigue, anxiety, and sleep disturbance. Higher pain was associated with greater fatigue, anxiety, and sleep disturbance, which in turn were associated with higher levels of depression. The largest mediating effect was through fatigue. Additional analyses excluded items with common content and suggested that the meditational effects observed were not attributable to content overlap across scales. Individuals living with MS who report high levels of chronic pain and depressive symptoms may benefit from treatment approaches that can address sleep, fatigue, and anxiety.

Chronic pain in multiple sclerosis: Is there also fibromyalgia? An observational study

BackgroundChronic pain is common in persons with multiple sclerosis (MS), but the co-morbidity of fibromyalgia (FM) has yet to be investigated in MS. Objectives of the study were to evaluate, among the various types of chronic pain, the frequency of FM in MS and its impact on MS patients’ health-related quality of life (HRQoL).Material/Methods133 MS patients were investigated for the presence and characterization of chronic pain within 1 month of assessment. A rheumatologist assessed the presence FM according to the 1990 ACR diagnostic criteria. Depression, fatigue, and HRQoL were also assessed by means of specific scales.ResultsChronic pain was present in 66.2% of patients (musculoskeletal in 86.3%; neuropathic in 13.7%; absent in 33.8% [called NoP]). Pain was diagnosed with FM (PFM+) in 17.3% of our MS patients, while 48.9% of them had chronic pain not FM type (PFM−); the prevalence of neuropathic pain in these 2 sub-groups was the same. PFM+ patients were prevalently females and had a higher EDSS than NoP. The PFM+ patients had a more pronounced depression than in the NoP group, and scored the worst in both physical and mental QoL.ConclusionsIn our sample of MS patients we found a high prevalence of chronic pain, with those patients displaying a higher disability and a more severe depression. Moreover, FM frequency, significantly higher than that observed in the general population, was detected among the MS patients with chronic pain. FM occurrence was associated with a stronger impact on patients’ QoL.

Further Evaluation of the Motivational Model of Pain Self-Management: Coping with Chronic Pain in Multiple Sclerosis

Growing evidence suggests that motivation to engage in pain-coping strategies is a key predictor of how well a person adjusts to pain. According to the Motivational Model of Pain Self-Management, readiness to engage in pain self-management behaviors is influenced by beliefs about the importance of the behavior (importance) and the ability to carry out the behavior (self-efficacy). The purpose of this study was to test the Motivational Model of Pain Self-Management for exercise and task persistence pain-coping behaviors in a sample of 114 individuals with multiple sclerosis and chronic pain. Measures included the Multidimensional Pain Readiness to Change Questionnaire-2 and measures of importance, self-efficacy, and coping behavior duration. Tests of mediation were conducted with two path analyses, one for each coping behavior. The effects of importance and self-efficacy beliefs on coping behaviors were mediated or partially mediated by readiness to engage in those behaviors. These findings provide support for the Motivational Model of Pain Self-Management and have important implications for the development of treatments for chronic pain.

Effects of levetiracetam on chronic pain in multiple sclerosis: results of a pilot, randomized, placebo‐controlled study

Central neuropathic pain (CNP) is a prevalent and distressing symptom in patients with multiple sclerosis (MS). The anticonvulsant levetiracetam (LEV) has been shown to be efficacious in some types of CNP, but its efficacy in MS-related CNP has not been confirmed. To investigate the tolerability and potential effects of LEV against CNP in MS subjects, we performed a single-center, prospective, randomized, single-blind, placebo-controlled study in twenty patients with MS and CNP. Outcomes before and during the 3-month study were assessed using validated measures of pain, depression, disability and quality of life. The medication was well tolerated and analysis revealed a significant difference between the LEV and placebo arm in all study outcomes related to pain (mean pain intensity score, mean pain difference, percentage of patients with a clinically significant pain reduction). Furthermore, the individual quality of life rating improved in treated patients, showing a significant correlation with pain reduction. These findings suggest that further studies with larger samples of patients be carried out in order to confirm the efficacy of LEV in MS-related CNP population.

Neuropathic pain behaviours in a chronic-relapsing model of experimental autoimmune encephalomyelitis (EAE)

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). While the primary symptoms of MS are losses of sensory and motor functions, it is now recognized that chronic pain is also a major concern affecting between 50% and 80% of MS patients. To date, however, few studies have examined the underlying mechanisms of chronic pain in MS or in the animal model, experimental autoimmune encephalomyelitis (EAE), which shares many features of MS pathology. We, therefore, set out to characterize the changes in pain sensitivity that arises in a chronic-relapsing model of EAE. We show here that female C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein (MOG35–55) develop a robust allodynia to both cold and tactile stimuli. Allodynia emerges early in the disease process, often before any signs of neurological deficit and is independent of the overall symptom severity in these mice. “Classical” cellular substrates for neuropathic pain and allodynia such as altered expression of sensory neuropeptides in the dorsal horn of the spinal do not appear to underlie these changes in sensory function. There is, however, a significant influx of CD3+ T cells and increased astrocyte and microglia/macrophage reactivity in the superficial dorsal horn of mice with MOG35–55 EAE. This suggests that inflammation and reactive gliosis may be key mediators of allodynia in MOG35–55 EAE similar to peripheral nerve and spinal cord injury models. Taken together, our results show that the MOG35–55 EAE model is a useful tool to study neuropathic pain in MS.

Chronic Pain in Multiple Sclerosis: Prevalence, Characteristics, and Impact on Quality of Life in an Australian Community Cohort

This cross-sectional study describes chronic pain in 94 persons with multiple sclerosis residing in the community. The characteristics of chronic pain, pain-related disability, pain treatments, barriers to health care, and impact on quality of life were examined. Sixty-four percent of participants reported chronic pain; of these, 60% had dysesthetic pain and 70% had episodic increases in pain. The mean numerical pain intensity rating score was moderate (5). Chronic Pain Grade was used to classify severity of pain, using scores for items for pain intensity and pain-related disability. Those in the higher pain grades had more disability and recorded more health care visits (P = .06) (not significant because of small sample size). Effective pain management techniques included analgesic medication and physical measures as reported by 54% and 44% participants, respectively. Participants' perceived barriers to health care included environmental and personal factors. Those with multiple sclerosis and pain, compared with those with no pain, showed a significant difference in the domain of psychological well-being scores (P = .01) on the Assessment of Quality of Life scale. Additionally, the domains of independent living (P = .009) and total scores (P = .04) showed better quality of life in participants with lower pain grades. Improved understanding of chronic pain in this population may facilitate early identification for timely intervention and minimize pain-related disability. This article describes chronic pain in persons with multiple sclerosis living in the community. The information regarding pain prevalence, pain-related disability, and impact on quality of life provides insight into the complex multidimensional pain experience. Improved understanding of pain and early intervention may contribute to the overall well-being and decrease pain-related disability in this population.