Pain in multiple sclerosis

MS is a disorder of the central nervous system white matter, usually presenting first in young adulthood. It is most commonly in a relapsing and remitting form, although for many it eventually becomes a progressive disorder. Even for those for whom it does not become progressive, there is often an accumulation of functional deficits. While the prognosis is variable, 50 percent will require ambulatory assistance within 15 years of disease onset.11 The median estimate of the prevalence of MS is reported as 0.9 per 1000 overall and 2 per 1000 in North America.12 That would mean that based on estimated May 2007 population numbers, in the United States alone 270,000-600,000 people are afflicted with MS.

As MS lesions can occur supratentorially, infra-tentorially (in the brain stem), or in the spinal cord, their associated clinical picture can be quite varied. Estimates of the prevalence of pain in MS, like other central pain syndromes, is complicated by poor delineation in most studies between types of pain. Estimates range from 29 percent13 to ^80 percent.14,15 However, most prevalence estimates (for all pain) fall within the 43-70 percent

range. , , , , , , , , , Variations in reported prevalence estimates can be attributed to the definition of MS-related pain (most studies exclude headache), patient populations assessed (MS rehabilitation center inpa-tients22 to outpatient MS clinics16,17 to population-based studies14), and survey methods used.18,21

Pain has been noted to be one of the cardinal presenting features of MS (either alone or in combination with other symptoms) in 5.5-10 percent of all MS

patients

It has been suggested that of those who would later be definitively identified as having central neuropathic or chronic pain (^20 percent), a higher percentage have pain as a presenting feature of their MS -i.e. when pain is part of the presenting complex of MS, chronic and central pain are more likely in the future.16,20

Few studies have delineated nociceptive pain from central neuropathic pain and neuropathic pain subtypes in these estimates. Those that have are important.

Osterberg et al.16 were thorough in their assessment of pain subtypes. Of their cohort of 364 MS patients, 57.5 percent reported pain during the course of their disease, 27.5 percent had central neuropathic pain (including 5 percent with trigeminal neuralgia). This most commonly affected the lower extremities (87 percent) (upper extremities in 31 percent) and was bilateral and constant (76 percent) (these data are very similar to Moulin et al.19). Interestingly, only 2 percent had paroxysmal pain and only 1 percent had spasticity-related pain. Others have found higher prevalences of paroxysmal pains identifying Lhermitte's sign as a bothersome pain in 9 percent17 and painful tonic leg spasms in 10

percent

One-third of those with central pain in

Osterberg's series reported multiple central pain loci with different onsets, modalities, and severity. Others have also found multiple pain types in MS to be not uncommon14,17 and in fact it may be more the rule than the exception.18 Nociceptive pain was evident in 21 percent in Osterberg's series,16 while back pain was seen in 14-18 percent of Solaro's and Moulin's series17,19 and

40 percent (similar to that in the general population) of Svendsen's population-based study.14 Joint pain was more common in MS patients than in the general Danish population.14

As in the other central pain syndromes, pain in MS was often severe (one-quarter of those reporting pain in one study18 and, in another study, one-third reported it as one of the worst symptoms of MS20). In a population-based study from Denmark, while the prevalence of pain in the previous month did not differ in a MS cohort from the general population, MS patients had higher pain intensity levels and were more likely to report pain that interfered with their daily life.14 In comparison with other chronic pain types, Ehde et al.18 found MS pain to be more severe than in a US population sample, although less severe than pain problems in SCI cohorts. MS pain severity was similar to that in rheumatoid and osteoarthritis cohorts and MS-related neuropathic pain was more severe than MS-related nociceptive pain.21 One-quarter of MS patients use daily analgesics (versus 9 percent of the general Danish population),14 yet it has also been shown that relative to pain severity and frequency, MS related pain is un- or undertreated.21 In keeping with other chronic pain states, pain in MS interferes with sleep, recreational activities, and work inside and outside the home.18

Osterberg et al. found central neuropathic pain to have the highest prevalence in the first 20 years of MS, thereafter decreasing. This differs from many other studies that have suggested chronic pain increases in prevalence with

13 17 19 20

increasing disease duration. , , , Others have not found this correlation.14,18,21,25 Most of these other studies have not defined specific pain types in assessing this correlation. Over time, MS patients often have accumulating functional deficits and it is in this setting that one would anticipate increasing prevalence of noci-ceptive/musculoskeletal pain complaints. Musculoskeletal pain prevalence has been shown to increase as soon as ambulatory assistance became necessary in MS patients.22 This apparent discrepancy - higher likelihood of central neuropathic pain in the first two decades of MS, and likely higher prevalence of musculoskeletal pain in latter years with increasing functional burdens - may be the result of prior study limitations and failure to delineate pain types.

Multiple studies have reported a correlation with the prevalence of MS-related pain with clinical spasticity or myelopathy,19,20 even if pain directly from the spasticity is uncommon in MS.16 This speaks to the pathogenesis of central neuropathic pain where most cases seem to have evidence of spinothalamic tract dysfunction (98 percent of those with MS-related central neuropathic pain).16 Hence spasticity and myelopathy are indicators of a disease process localizing to the spinal cord and with higher likelihood of also affecting the spinothalamic tracts which are etiologically important for central pain.

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