Pain associated with multiple sclerosis: Systematic review and proposed classification

Department of Medicine, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Pain (Impact Factor: 5.21). 08/2008; 137(1):96-111. DOI: 10.1016/j.pain.2007.08.024
Source: PubMed


Pain is common in patients with multiple sclerosis (MS), but estimates of its prevalence have varied widely. The literature describing pain in MS patients spans four decades and has employed a range of different methodologies. We undertook a systematic review in order to summarize current understanding of the association between MS and pain and provide a basis for the design and interpretation of future studies. The point prevalence of pain in patients with MS is nearly 50%, and approximately 75% of patients report having had pain within one month of assessment. Pain adversely affects most aspects of health-related quality of life, including functional domains such as the ability to work. The presence of pain in patients with MS is associated with increased age, duration of illness, depression, degree of functional impairment, and fatigue. Several different types of pain are found in patients with MS, including extremity pain, trigeminal neuralgia, Lhermitte's sign, painful tonic spasms, back pain, and headache. Putative mechanisms of pain in patients with MS are discussed, and a classification of pain in MS is proposed. Few randomized clinical trials of treatments for MS pain have been conducted, and the limitations of current knowledge regarding approaches for treating MS pain are discussed. Suggestions for future studies that would increase understanding of the natural history, mechanisms, and treatment of pain in patients with MS are presented.

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Available from: John Markman, Jan 06, 2015
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    • "Recently, special attention has been paid on the diagnosis and management of these symptoms. Painful syndromes encountered in MS patients have been well described and divided in four major categories: trigeminal neuralgia , spasticity, neuropathic and musculoskeletal pain syndromes [12]. In addition, depression and anxiety usually associated with chronic health problems have been investigated over the last few years. "
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    ABSTRACT: Multiple sclerosis (MS) is a disabling neurological disorder presenting a variety of symptoms which are hard to control by actual drug regimens. Non-invasive brain stimulation (NIBS) techniques have been investigated in the past years for the improvement of several neurologic and psychiatric disorders. Here, we review the application of transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS, including the theta burst stimulation variant) and electroconvulsive therapy (ECT) in MS patients. The results of tDCS and rTMS for the treatment of pain, tactile sensory deficit, motor performance, fatigue, and spasticity were assessed in several studies, but the data are sparse and insufficient to conclude definitively at an efficacy of some protocols of tDCS or rTMS. On the other hand, ECT was shown to be efficacious for the treatment of severe psychiatric disorders associated with MS in 21 case reports, but controlled trials are lacking. Therefore, more studies are still needed to better define the place and potential role of NIBS in the treatment of various neurological and psychiatric symptoms frequently occurring in MS.
    Brain Stimulation 10/2014; 7(6). DOI:10.1016/j.brs.2014.09.014 · 4.40 Impact Factor
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    • "Further subdivision into nine categories has been suggested based upon the proposed underpinning mechanisms (Truini et al. 2013). Herein, we have reviewed research on the most common MS-related neuropathic pain conditions including ongoing pain in the extremities (dysaesthetic extremity pain), as well as paroxysmal pain (trigeminal neuralgia and L’hermitte’s phenomenon) (O’Connor et al. 2008; Truini et al. 2013). "
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    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.
    Inflammopharmacology 11/2013; 22(1). DOI:10.1007/s10787-013-0195-3
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    • "For example, injection of a TH1 cell population producing pro-inflammatory cytokines increased the level of neuropathic pain, whereas injection of a TH2 cell population producing anti-inflammatory cytokines attenuated pain sensitivity in nerve-injured rats (15). As chronic neuropathic pain affects the majority of MS patients (10, 17), it is believed that modulation of pro-inflammatory T cells and their associated cytokine response will mitigate such symptoms. "
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    ABSTRACT: Neuropathic pain is a chronic symptom of multiple sclerosis (MS) and affects nearly half of all MS sufferers. A key instigator of this pain is the pro-inflammatory response in MS. We investigated the behavioral effects of immunization with a mutant peptide of myelin basic protein (MBP), termed altered peptide ligand (APL), known to initiate immune deviation from a pro-inflammatory state to an anti-inflammatory response in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Male and female Lewis rats were injected with vehicle control or with varying doses of 50 or 100 μg guinea pig MBP in combination with or without APL. APL-treated animals established significantly lower disease severity compared to encephalitogenic MBP-treated animals. Animals with EAE developed mechanical, but not thermal pain hypersensitivity. Mechanical pain sensitivities were either improved or normalized during periods of clinical disease in male and female APL-treated animals as compared to the encephalitogenic group. No significant changes to thermal latency were observed upon co-immunization with APL. Together these data indicate that APL ameliorates disease states and selectively mediates an analgesic effect on EAE animals.
    Frontiers in Neurology 10/2013; 4:168. DOI:10.3389/fneur.2013.00168
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