Pain In Multiple Sclerosis Research Articles

Neuropathic Pain Secondary to Multiple Sclerosis: A Narrative Review.

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS). Neuropathic pain in MS is a debilitating symptom that significantly impairs the quality of life for a substantial proportion of MS patients. Neuropathic pain in MS stems primarily from demyelination, axonal loss, CNS inflammation, and direct damage to the myelin sheath, leading to pain manifestations such as ongoing extremity pain, Lhermitte's phenomenon, and trigeminal neuralgia (TN). The pathophysiological mechanisms behind MS-related neuropathic pain are explored in this review, highlighting central sensitization, neural dysfunction, spinal thalamic tract dysfunction, and inflammatory processes that exacerbate neuronal damage. Neuropathic pain in MS necessitates comprehensive assessment tools and neurophysiological tests to differentiate neuropathic pain from other MS symptoms accurately. Treatment strategies for MS-related neuropathic pain encompass pharmacological interventions, including anticonvulsants and antidepressants, and emerging therapies targeting specific inflammatory processes. The review advocates for a holistic approach to management, incorporating innovative treatments and multidisciplinary strategies to address both the physical symptoms and psychosocial aspects of this disorder. This comprehensive overview underscores the importance of ongoing research into targeted therapies to improve patient outcomes and enhance the quality of life for those affected by MS.

Emotional burden among MS patients: associations between specific chronic pain diagnoses and psychological features.

Central neuropathic pain (CNP) and musculoskeletal pain (MSP) are often comorbid with multiple sclerosis (MS), yet data on the emotional burden entailed by this comorbidity are very limited. We studied whether MS patients with CNP exhibited greater emotional burden and pain severity than those with MSP and whether this emotional burden was attributed to the MS, the chronic pain, or both. Participants were 125 MS patients (55 with CNP; 30 with MSP; 40 MS pain-free) and 30 healthy controls (HCs). Participants completed questionnaires assessing pain interference, pain catastrophizing, depression, anxiety, stress, hypervigilance, and chronic pain. Group comparisons and a two-step cluster analysis were performed, and the association between cluster membership and clinical group membership was evaluated. Chronic pain was stronger and more widespread in the CNP group than in the MSP group. Both pain groups had higher pain interference, pain catastrophizing, and stress compared to MS pain-free and HC groups. All MS groups had greater depression levels compared to HCs, and the CNP group had the highest anxiety level. The "high psychological distress" cluster comprised mainly participants with CNP (57%), and the "minimal psychological distress" cluster comprised mainly the MS pain-free and HC groups. In conclusion, CNP seems to induce greater emotional burden and pain severity than does MSP. Whereas depression may be attributed to MS, and anxiety to CNP, enhanced pain interference, catastrophizing, and stress may be attributed to the comorbidity of MS and chronic pain. Identifying these traits among MS patients and targeting them in management programs may contribute to more effective, individually based care.

Self-reported fatigue impact is associated with frequency of falls and injurious falls in people with multiple sclerosis.

Fatigue is the most common symptom associated with multiple sclerosis (MS). Fatigue as a risk factor for injurious falls and frequency of falls is understudied. Falling recurrently is associated with injurious falls which may lead to reduced functional independence and poor quality of life of people with MS. Identifying contributors of recurrent falls and injurious falls is clinically useful to develop effective interventions. To investigate the associations between fatigue impact and frequency of falls and injurious falls in people with MS. Fifty-one participants completed the Modified Fatigue Impact Scale (MFIS) and a survey of number of falls and injurious falls during the past year. Logistic regression analyses were conducted to investigate whether scores on the MFIS (Total, Physical, Cognitive, and Psychosocial) predicted odds of being a recurrent faller (> 2 falls) or infrequent faller (1- 2 falls) versus a non-faller, and odds of experiencing an injurious fall (yes/no). The analyses were adjusted for demographic and clinical characteristics and common symptoms of MS (depression, cognition, pain, and sleep disturbance). Higher MFIS Total score was associated with higher odds of infrequent falls (OR=1.07, 95% CI, 1.00 - 1.15, p=0.05) and recurrent falls (OR=1.10, 95% CI, 1.00 - 1.20, p=0.04) relative to not falling in the past year. Higher scores on the MFIS Physical subscale were significantly associated with high odds of infrequent falls (OR=1.15, 95% CI, 1.02 - 1.30, p=0.03) and recurrent falls (OR=1.19, 95% CI, 1.02 - 1.39, p=0.03). MFIS Psychosocial subscale was significantly associated with higher odds of infrequent falls (OR=2.01, 95% CI, 1.14 - 3.53, p=0.02). MFIS Total and MFIS Cognitive subscale were significantly associated with higher odds of injurious falls (OR=1.11, 95% CI, 1.00 - 1.23, p=0.04) and (OR=1.28, 95% CI, 1.02 - 1.60, p=0.04), respectively. The findings indicated self-reported fatigue impact and its specific domains were associated with an increased risk of falling and injurious falls. Further studies using prospective falls assessment and longitudinal evaluation of fatigue are warranted to extend our findings.

Lower corticospinal excitability and greater fatigue among people with multiple sclerosis experiencing pain.

Persons with multiple sclerosis (MS) frequently report pain that negatively affects their quality of life. Evidence linking pain and corticospinal excitability in MS is sparse. We aimed to (1) examine differences in corticospinal excitability in MS participants with and without pain and (2) explore predictors of pain. Sixty-four participants rated their pain severity on a visual analog scale (VAS). Transcranial magnetic stimulation (TMS) and validated clinical instruments characterized corticospinal excitability and subjective disease features like mood and fatigue. We retrieved information on participants' prescriptions and disability status from their clinical records. Fifty-five percent of participants reported pain that affected their daily functioning. Persons with pain had significantly greater fatigue and lower area under the excitatory motor evoked potential (MEP) recruitment curve (eREC AUC), a measure of total corticospinal excitability. After controlling for age, disability status, and pain medications, increased fatigue and decreased eREC AUC together explained 40% of the variance in pain. Pain in MS is multifactorial and relates to both greater fatigue and lesser corticospinal excitability. Future work should better characterize relationships between these outcomes to develop targeted pain interventions such as neuromodulation. We examined pain in MS. Individuals with pain had higher fatigue and lower corticospinal excitability than those without pain. These outcomes significantly predicted self-reported pain.

Sex differences in the inflammatory response of the mouse DRG and its connection to pain in experimental autoimmune encephalomyelitis

Multiple Sclerosis (MS) is an autoimmune disease with notable sex differences. Women are not only more likely to develop MS but are also more likely than men to experience neuropathic pain in the disease. It has been postulated that neuropathic pain in MS can originate in the peripheral nervous system at the level of the dorsal root ganglia (DRG), which houses primary pain sensing neurons (nociceptors). These nociceptors become hyperexcitable in response to inflammation, leading to peripheral sensitization and eventually central sensitization, which maintains pain long-term. The mouse model experimental autoimmune encephalomyelitis (EAE) is a good model for human MS as it replicates classic MS symptoms including pain. Using EAE mice as well as naïve primary mouse DRG neurons cultured in vitro, we sought to characterize sex differences, specifically in peripheral sensory neurons. We found sex differences in the inflammatory profile of the EAE DRG, and in the TNFα downstream signaling pathways activated intracellularly in cultured nociceptors. We also found increased cell death with TNFα treatment. Given that TNFα signaling has been shown to initiate intrinsic apoptosis through mitochondrial disruption, this led us to investigate sex differences in the mitochondria’s response to TNFα. Our results demonstrate that male sensory neurons are more sensitive to mitochondrial stress, making them prone to neuronal injury. In contrast, female sensory neurons appear to be more resistant to mitochondrial stress and exhibit an inflammatory and regenerative phenotype that may underlie greater nociceptor hyperexcitability and pain. Understanding these sex differences at the level of the primary sensory neuron is an important first step in our eventual goal of developing sex-specific treatments to halt pain development in the periphery before central sensitization is established.

The Efficacy of Cannabis on Multiple Sclerosis-Related Symptoms.

Multiple sclerosis (MS) is known as an autoimmune disease that damages the neurons in the central nervous system. MS is characterized by its most common symptoms of spasticity, muscle spasms, neuropathic pain, tremors, bladder dysfunction, dysarthria, and some intellectual problems, including memory disturbances. Several clinical studies have been conducted to investigate the effects of cannabis on the relief of these symptoms in MS patients. The efficacy of Cannabis sativa (C. Sativa) in the management of MS outcomes such as spasticity, pain, tremors, ataxia, bladder functions, sleep, quality of life, and adverse effects were assessed in this review. Most clinical studies showed the positive effects of cannabinoids with their different routes of administration, such as oromucosal spray and oral form, in reducing most MS symptoms. The oromucosal spray Nabiximols demonstrated an improvement in reducing MS spasticity, pain, and quality of life with a tolerated adverse effect. Oral cannabinoids are significantly effective for treating MS pain and spasticity, while the other symptoms indicate slight improvement and the evidence is quite inconsistent. Oromucosal spray and oral cannabis are mainly used for treating patients with MS and have positive effects on treating the most common symptoms of MS, such as pain and spasticity, whereas the other MS symptoms indicated slight improvement, for which further studies are needed.

Neuropathic Pain in Multiple Sclerosis and Its Animal Models: Focus on Mechanisms, Knowledge Gaps and Future Directions

Multiple sclerosis (MS) is a multifaceted, complex and chronic neurological disease that leads to motor, sensory and cognitive deficits. MS symptoms are unpredictable and exceedingly variable. Pain is a frequent symptom of MS and manifests as nociceptive or neuropathic pain, even at early disease stages. Neuropathic pain is one of the most debilitating symptoms that reduces quality of life and interferes with daily activities, particularly because conventional pharmacotherapies do not adequately alleviate neuropathic pain. Despite advances, the mechanisms underlying neuropathic pain in MS remain elusive. The majority of the studies investigating the pathophysiology of MS-associated neuropathic pain have been performed in animal models that replicate some of the clinical and neuropathological features of MS. Experimental autoimmune encephalomyelitis (EAE) is one of the best-characterized and most commonly used animal models of MS. As in the case of individuals with MS, rodents affected by EAE manifest increased sensitivity to pain which can be assessed by well-established assays. Investigations on EAE provided valuable insights into the pathophysiology of neuropathic pain. Nevertheless, additional investigations are warranted to better understand the events that lead to the onset and maintenance of neuropathic pain in order to identify targets that can facilitate the development of more effective therapeutic interventions. The goal of the present review is to provide an overview of several mechanisms implicated in neuropathic pain in EAE by summarizing published reports. We discuss current knowledge gaps and future research directions, especially based on information obtained by use of other animal models of neuropathic pain such as nerve injury.

TNFα in MS and Its Animal Models: Implications for Chronic Pain in the Disease.

Multiple Sclerosis (MS) is a debilitating autoimmune disease often accompanied by severe chronic pain. The most common type of pain in MS, called neuropathic pain, arises from disease processes affecting the peripheral and central nervous systems. It is incredibly difficult to study these processes in patients, so animal models such as experimental autoimmune encephalomyelitis (EAE) mice are used to dissect the complex mechanisms of neuropathic pain in MS. The pleiotropic cytokine tumor necrosis factor α (TNFα) is a critical factor mediating neuropathic pain identified by these animal studies. The TNF signaling pathway is complex, and can lead to cell death, inflammation, or survival. In complex diseases such as MS, signaling through the TNFR1 receptor tends to be pro-inflammation and death, whereas signaling through the TNFR2 receptor is pro-homeostatic. However, most TNFα-targeted therapies indiscriminately block both arms of the pathway, and thus are not therapeutic in MS. This review explores pain in MS, inflammatory TNF signaling, the link between the two, and how it could be exploited to develop more effective TNFα-targeting pain therapies.

Toll-like receptor 2 and 4 antagonism for the treatment of experimental autoimmune encephalomyelitis (EAE)-related pain

Neuropathic pain is a major symptom of multiple sclerosis (MS) with up to 92% of patients reporting bodily pain, and 85% reporting pain severe enough to cause functional disability. None of the available therapeutics target MS pain. Toll-like receptors 2 and 4 (TLR2/TLR4) have emerged as targets for treating a wide array of autoimmune disorders, including MS, as well as having demonstrated success at suppressing pain in diverse animal models. The current series of studies tested systemic TLR2/TLR4 antagonists in males and females in a low-dose Myelin oligodendrocyte glycoprotein (MOG) experimental autoimmune encephalomyelitis (EAE) model, with reduced motor dysfunction to allow unconfounded testing of allodynia through 50+ days post-MOG. The data demonstrated that blocking TLR2/TLR4 suppressed EAE-related pain, equally in males and females; upregulation of dorsal spinal cord proinflammatory gene expression for TLR2, TLR4, NLRP3, interleukin-1β, IkBα, TNF-α and interleukin-17; and upregulation of dorsal spinal cord expression of glial immunoreactivity markers. In support of these results, intrathecal interleukin-1 receptor antagonist reversed EAE-induced allodynia, both early and late after EAE induction. In contrast, blocking TLR2/TLR4 did not suppress EAE-induced motor disturbances induced by a higher MOG dose. These data suggest that blocking TLR2/TLR4 prevents the production of proinflammatory factors involved in low dose EAE pathology. Moreover, in this EAE model, TLR2/TLR4 antagonists were highly effective in reducing pain, whereas motor impairment, as seen in high dose MOG EAE, is not affected.

Neurofeedback therapy for the management of multiple sclerosis symptoms: current knowledge and future perspectives.

Fatigue is a frequent and debilitating symptom in patients with multiple sclerosis (MS). Affective manifestations are also of high prevalence in this population and can drastically impact the patients' functioning. A considerable proportion of patients with MS suffer from cognitive deficits affecting general and social cognitive domains. In addition, pain in MS is commonly observed in neurology wards, could be of different types, and may result from or be exacerbated by other MS comorbidities. These complaints tend to cluster together in some patients and seem to have a complex pathophysiology and a challenging management. Exploring the effects of new interventions could improve these outcomes and ameliorate the patients' quality of life. Neurofeedback (NFB) might have its place in this context by enhancing or reducing the activity of some regions in specific electroencephalographic bands (i.e., theta, alpha, beta, sensorimotor rhythm). This work briefly revisits the principles of NFB and its application. The published data are scarce and heterogeneous yet suggest preliminary evidence on the potential utility of NFB in patients with MS (i.e., depression, fatigue, cognitive deficits and pain). NFB is simple to adapt and easy to coach, and its place in the management of MS symptoms merits further investigations. Comparing different NFB protocols (i.e., cortical target, specific rhythm, session duration and number) and performing a comprehensive evaluation could help developing and optimizing interventions targeting specific symptoms. These aspects could also open the way for the association of this technique with other approaches (i.e., brain stimulation, cognitive rehabilitation, exercise training, psychotherapies) that have proved their worth in some MS domains.

Characterizing chronic pain phenotypes in multiple sclerosis: a nationwide survey study.

Chronic pain is highly prevalent in multiple sclerosis (MS). Pain heterogeneity may contribute to poor treatment outcomes. The aim of this study was to characterize pain phenotypes distributions in persons with MS and compare pain phenotypes in terms of pain intensity, frequency of chronic overlapping pain conditions, and use and analgesic effects of different classes of pain medications. Data were collected through a national web-based survey with measures of neuropathic (painDETECT) and nociplastic pain (Fibromyalgia Survey Criteria), chronic overlapping pain conditions, and pain medication use and pain relief. In a sample of N = 842 adults with chronic pain and MS, the largest proportion (41%) showed evidence of nociceptive pain, 27% had mixed neuropathic/nociplastic pain, 23% had nociplastic pain, and 9% had neuropathic pain. Nociplastic pain was associated with significantly higher pain intensity and frequency of chronic overlapping pain conditions. Across all pain types, high frequency of pain medication use along with poor-modest pain relief was reported. Cannabis use for pain was more common, and pain relief ratings were higher among those with nociplastic pain, relative to nociceptive pain. Although NSAID use was highest among those with nociplastic pain (80%), pain relief ratings for NSAIDs were highest among those with nociceptive pain. These findings underscore the need for multidimensional assessment of pain in MS with greater emphasis on the identification of pain phenotype. An improved characterization of pain as a multifaceted condition in MS could inform therapeutic approaches.

Smartphone based behavioral therapy for pain in multiple sclerosis (MS) patients: A feasibility acceptability randomized controlled study for the treatment of comorbid migraine and ms pain

BackgroundMultiple Sclerosis (MS) and Migraine are comorbid neurologic conditions. Migraine prevalence is three times higher in the MS clinic population compared to the general population, and patients with MS and migraine are more symptomatic than patients with MS without migraine. ObjectiveWe sought to conduct a pilot feasibility and acceptability study of the RELAXaHEAD app in MS-Migraine patients and to assess whether there was any change in migraine disability and MS pain-related disability. MethodsRandomized controlled study of patients with MS-migraine ages 18–80 years with 4+ headache days/ month who were willing to engage in smartphone based behavioral therapy. Half received the RELAXaHEAD app with progressive muscle relaxation (PMR) and the other half received the app without the PMR. Data was collected for 90 days on measures of recruitment, retention, engagement, and adherence to RELAXaHEAD. Preliminary data was also collected on migraine disability (MIDAS) and MS pain (PES). ResultsSixty-two subjects with MS-migraine were enrolled in the study (34 in PMR arm, 28 in monitored usual care arm). On average, during the 90 days, participants played the PMR on average 1.8 times per week, and for 12.9 min on days it was played. Forty-one percent (14/34) of the participants played the PMR two or more times weekly on average. Data was entered into the daily diaries, on average, 49% (44/90) of the days. There were major challenges in reaching subjects in follow-up for the efficacy data, and there was no significant change in migraine disability (MIDAS) scores or MS Pain (PES) scores from baseline to the endpoints. During the six-month follow-up, most patients felt either positively or neutral about the relaxation therapy. ConclusionThere was interest in scalable accessible forms of behavioral therapy to treat migraine and MS-related pain in patients with MS and comorbid migraine. Similar to prior studies, a significant minority were willing to practice the PMR at least twice weekly. In the societal shift from telephone to more text and internet-based interactions, follow up was challenging, but those reached indicated that they appreciated the PMR and would recommend it to others. Future work should focus on engagement and efficacy.

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.

Effectiveness of monopolar dielectric transmission of pulsed electromagnetic fields for multiple sclerosis–related pain: a pilot study

IntroductionPain is highly prevalent in patients with multiple sclerosis (MS); it is chronic in 50% of cases and is classified as nociceptive, neuropathic, or mixed-type. Pain affects quality of life, sleep, and the activities of daily living. Electrotherapy is an interesting alternative or complementary treatment in the management of pain in MS, with new innovations constantly appearing. Material and methodsThis study evaluates the effectiveness of treatment with monopolar dielectric transmission of pulsed electromagnetic fields (PEMF) for pain associated with MS. We performed a randomised, placebo-controlled clinical trial including 24 patients, who were assessed with the Brief Pain Inventory, the Multiple Sclerosis International Quality of Life questionnaire, the Beck Depression Inventory, and the Modified Fatigue Impact Scale. ResultsStatistically significant improvements were observed in maximum and mean pain scores, as well as in the impact of pain on work, personal relationships, and sleep and rest. Not significant differences were found between the treatment and placebo groups. ConclusionsTreatment with PEMF may be effective in reducing pain in patients with MS, although further research is necessary to confirm its effectiveness over placebo and to differentiate which type of pain may be more susceptible to this treatment.

Longitudinal prevalence and determinants of pain in multiple sclerosis: results from the German National Multiple Sclerosis Cohort study.

Pain is frequent in multiple sclerosis (MS) and includes different types, with neuropathic pain (NP) being most closely related to MS pathology. However, prevalence estimates vary largely, and causal relationships between pain and biopsychosocial factors in MS are largely unknown. Longitudinal studies might help to clarify the prevalence and determinants of pain in MS. To this end, we analyzed data from 410 patients with newly diagnosed clinically isolated syndrome or relapsing-remitting MS participating in the prospective multicenter German National MS Cohort Study (NationMS) at baseline and after 4 years. Pain was assessed by self-report using the PainDETECT Questionnaire. Neuropsychiatric assessment included tests for fatigue, depression, and cognition. In addition, sociodemographic and clinical data were obtained. Prevalence of pain of any type was 40% and 36% at baseline and after 4 years, respectively, whereas prevalence of NP was 2% and 5%. Pain of any type and NP were both strongly linked to fatigue, depression, and disability. This link was even stronger after 4 years than at baseline. Moreover, changes in pain, depression, and fatigue were highly correlated without any of these symptoms preceding the others. Taken together, pain of any type seems to be much more frequent than NP in early nonprogressive MS. Moreover, the close relationship between pain, fatigue, and depression in MS should be considered for treatment decisions and future research on a possible common pathophysiology.

Cognitive Behavioral Therapy for the Management of Multiple Sclerosis-Related Pain: A Randomized Clinical Trial.

Pain is a common and often debilitating symptom in persons with multiple sclerosis (MS). Besides interfering with daily functioning, pain in MS is associated with higher levels of depression and anxiety. Although cognitive behavioral therapy (CBT) for pain has been found to be an effective treatment in other populations, there has been a dearth of research in persons with MS. Persons with MS with at least moderate pain severity (N = 20) were randomly assigned to one of two groups: CBT plus standard care or MS-related education plus standard care, each of which met for 12 sessions. Changes in pain severity, pain interference, and depressive symptom severity from baseline to 15-week follow-up were assessed using a 2×2 factorial design. Participants also rated their satisfaction with their treatment and accomplishment of personally meaningful behavioral goals. Both treatment groups rated their treatment satisfaction as very high and their behavioral goals as largely met, although only the CBT plus standard care group's mean goal accomplishment ratings represented significant improvement. Although there were no significant differences between groups after treatment on the three primary outcomes, there was an overall improvement over time for pain severity, pain interference, and depressive symptom severity. Cognitive behavioral therapy or education-based programs may be helpful adjunctive treatments for persons with MS experiencing pain.

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.

Pain Management in Multiple Sclerosis: a Review of Available Treatment Options.

Multiple Sclerosis (MS) is a chronic autoimmune disease with no curative treatment available. While recent years have ushered in many effective new disease-modifying therapies for MS, they have not obviated the need for symptomatic treatments for MS-related pain. In this review, we discuss available approaches to control pain, which is one of the most common complaints MS patients have. The most recent research in this topic is directed towards non-pharmacologic interventions including water exercises, yoga and cannabis. More trials are being conducted on neuromodulation for MS-related neuropathic pain, including transcutaneous electrical nerve stimulation (TENS) and transcranial direct current stimulation (tDCS). Pain control for MS patients is challenging, considering the progressive and relapsing remitting nature of the disease, however, it is a very important aspect of it's management, as it improves mobility, exercise tolerance, concomitant depression and overall quality of life. Future research should focus on the use of neuromodulation in controlling MS pain.

The protective role of Hypericum perforatum in treatment of oxidative stress-induced multiple sclerosis is affected by extraction procedure: A literature review

Incidence of multiple sclerosis (MS) is increasing over all the world, because effective treatment of the disease has not been discovered yet. In the treatment of MS, different inflammatory chemical drugs have been used, but they have adverse effects on the normal cells and neurons, although plant extracts including Hypericum perforatum has no adverse effects on the normal cells in human. Oxidative stress induced excessive production of reactive oxygen species (ROS) and ROS production occurs during the several physiological and pathophysiological functions. Hypericum perforatum known as St. John’s Wort, has been proven to relieve in depression. However, results of recent studies reported modulator role of Hypericum perforatum on MS in rats (Nazıroğlu et al. 2014). The cellular and molecular mechanisms that underlie the effects of the Hypericum perforatum on MS pain pathways are not known, results in the literature suggest that the modulator effects of Hypericum perforatum in MS could be related to an increase antioxidant effect (Mojaverrostami et al. 2018). Recently, modulator roles of plant extracts such as Hypericum perforatum and through inhibition of ROS production in the treatment of MS have been reported. However, antioxidant contents of the plant extracts were affected by several factors, including extraction procedures (Dresler et al. 2018). In the presentation, I will review current data on&amp;nbsp;the extraction procedures of Hypericum perforatum. In addition, I will summarize recent data on therapeutic roles of Hypericum perforatum in MS.&amp;nbsp; &amp;nbsp;In conclusion, it seems that Hypericum perforatum has potential therapeutic effects against MS-induced oxidative stress.&amp;nbsp;

Prevalence of pain in patients with multiple sclerosis and its association with anxiety, depressive symptoms and quality of life.

Pain is one of the most frequently reported symptoms of multiple sclerosis (MS). It affects the daily functioning of patients, limits the ability to work and reduces the joy of life. The aim of the study was to analyze the impact of pain on quality of life as well as symptoms of anxiety and depression in patients with MS. The study included 144 patients with diagnosed MS (mean age 41±12 years, mean illness duration 10.3±8.6 years). The study was carried out on the basis of the author's survey on current and previous pain - the Quality of Life Self-esteem Questionnaire (EuroQol5D) and the Hospital Anxiety and Depression Scale (HADS). Among all respondents, 117 (81.3%) reported current pain, and 120 (83.3%) declared the occurrence of pain in the past. Currently, patients have reported: pain in one or more extremities - 79 people (54.9%), headache and facial pain - 72 (50%), back pain - 72 (50%), painful muscle spasms - 54 (38.6%), ocular pain - 37 (25.7%), Lhermitte's sign - 32 (22.2%). Patients reporting pain experienced significantly more severe symptoms of anxiety and depression (HADS-L: 8.0±4.3 vs. 5.1±4.3; p< 0.01; HADS-D: 6.0±4.2 vs. 3.4±3.7; p< 0.01), and had significantly worse quality of life (EQ 5D: 8.1±1.9 vs. 6.3±1.4; p< 0.0001). An association between presence of pain and gender (p< 0.01), age (p< 0.05), the degree of disability (p< 0.05), education (p< 0.001), and the professional activity (p< 0.01) was found. Pain in MS is associated with more severe symptoms of anxiety and depression, and worse quality of life. Female sex, older age, lower level of education, greater disability, and lack of occupational work predispose to the occurrence of pain in MS.