Neuropathic Pain in Multiple Sclerosis

Clinically isolated syndromes that are consistent with multiple sclerosis, and which may precede the diagnosis, are defined as a single episode of central nervous system dysfunction with partial or complete resolution. The presentation of a clinically isolated syndrome may not be pathognomonic for the disease, but can be highly suggestive, and may occur in young adults. Among these syndromes are syndromes associated with neuropathic pain, specifically radicular dysesthias and symptoms, and optic neuritis. While there are other clinically isolated syndromes that present as motor symptoms or problems with coordination, the treatment strategy for pain should take into consideration the possibility that the patient may go on to develop multiple sclerosis. Evidence is accumulating to suggest that initiation of disease-modifying therapies for these syndromes may delay conversion to frank multiple sclerosis. .

Commonly associated sensory symptoms frequently herald the development of multiple sclerosis. These dysesthesias include numbness, tightness, coldness, or a pins-and-needles feeling. Radicular pains can frequently occur. They are commonly noted in the abdominal and low thoracic region. In the cervical dermatomes, an intense unilateral pruritus is suggestive of MS. Transverse myelitis, which presents with rapid onset of weakness and dysfunction of bowel and bladder, is also associated with alterations in sensation. 

Ocular Pain in Multiple Sclerosis

Optic neuritis is a frequently occurring type of unilateral eye pain that is exacerbated by ocular movement, and is often followed by visual scotomas that may obscure the center of the visual field. . Optic neuritis is the most common type of ocular involvement in MS. The cumulative five-year incidence of clinically proven MS was 30 percent after an initial episode of idiopathic demyelinating optic neuritis, in the Optic Neuritis Treatment Trial (ONTT) 1 

Diagnostic Pearls

In typical clinically isolated syndromes, a patient may be diagnosed by the McDonald criteria. With atypical syndromes, MRI may be confirmatory of lesions separated in distance and time. Oligoclonal bands in patients with clinically isolated syndromes have been found to be associated with an increased risk of development of clinically definite multiple sclerosis. Serum antimyelin antibodies have been studied as potential markers of progression to MS in many instances of a clinically isolated syndrome, including pain syndromes. 

Management

Management of pain in cases in which an initial episode may be a typical clinically isolated syndrome that is likely to lead to progression with MS may be treated with recombinant human interferon beta, which can delay the occurrence of a second attack for as long as five years.2 Intravenous immunoglobulin may also improve long-term outcomes in patients with pain from a first demyelinating event. 

Acute Management of Optic Neuralgia

In addition to treatment with disease-modifying anti-rheumatic drugs to treat the etiology of the pain, symptomatic treatment is necessary. Because optic neuritis, an inflammatory and demyelinating condition that causes both visual loss and retrobulbar pain, is so frequently the presenting symptom of MS, there are various imaging tests to confirm the source of the pain and any associated loss of vision. Optic neuritis is normally a self-limited condition, but it is a condition that may take weeks or months to resolve. Intravenous methylprednisolone may resolve an exacerbation of optic neuritis, and is associated with rapid recovery of vision and delayed onset of multiple sclerosis, but has no effect on long-term visual loss. Oral prednisone is not recommended, as it may be associated with an increased risk of recurrence of optic neuritis.4 

Symptomatic Treatment of Pain

A variety of sources of painful symptoms in patients with MS were assessed in a large multicenter trial, with more than 43 percent of patients reporting painful symptoms, including trigeminal neuralgia in two percent of patients, dysesthetic pain in 18 percent, back pain in 16 percent, visceral pain in three percent, and painful tonic spasms in 11 percent of patients studied; nine percent of patients studied exhibited a Lhermitte sign. 5

Treatment of trigeminal neuralgia includes carbamazepine, which was found to be effective in four randomized, controlled trials of 147 patients.6,7,8,9 For those patients who fail treatment with carbamazepine, other medications, including baclofen10 and lamitrogine, have been effective.11 Some clinicians report that despite a lack of controlled data regarding the use of opioids in the treatment of trigeminal neuralgia, the pain may be made bearable while other treatments take effect.12 Botulinum toxin injections may also be beneficial for trigeminal neuralgia in patients who fail therapy with typical pharmacologic agents.13

Treatment of other types of chronic or long-term pain associated with multiple sclerosis may include the use of a variety of analgesics, including acetaminophen and nonsteroidal anti-inflammatory drugs. Tricyclic antidepressants have been used to treat various pain syndromes effectively, although study results have been conflicting.14

There is insufficient evidence available to determine the efficacy of skeletal muscle relaxants in restoration of functional impairment or in the treatment of pain in patients with MS.15 In the sole trial evaluating the use of a benzodiazepine available in the United States, diazepam, there was no difference in effectiveness between diazepam and placebo.16

Current evidence is available to demonstrate the benefits associated with the use of antiepileptic medications for treatment of patients with acute or subacute chronic back pain and neuropathic pain. For radicular pain, studies of gabapentin,17 pregabalin, 18 and topiramate19 each showed evidence of small incremental improvement in pain symptoms, but other studies were conflicting and showed no evidence of improvement in pain symptoms.

Nonpharmacologic Therapies for Pain in MS

Additional modalities of pain relief in patients with MS may include neuromodulation through external peripheral, internal peripheral, spinal, or supraspinal systems. The transcutaneous nerve stimulation system, or TENS unit, is a non-invasive system that utilizes application of low-voltage electrical current applied to the skin for pain relief. TENS treatments encompass a variety of different stimulation parameters. Most patients are able to safely apply the unit, but there are no rigorous randomized controlled trials that demonstrate the effectiveness of this modality of pain control. Systematic reviews have mixed results with respect to the efficacy of TENS.20  

Spinal cord stimulation is one option for chronic neuropathic pain. It is minimally invasive and reversible, or may be permanently implanted after efficacy is established. Spinal cord stimulation has shown demonstrable effectiveness in the treatment of complex regional pain syndromes in at least one European study.21

Deep brain stimulation is in the early stages of development, but anecdotal reports describe successful treatment of intractable severe pain.22

Behavioral Modalities of Pain Control

Behavioral modalities of treatment used for amelioration of chronic pain include biofeedback and cognitive behavioral therapy, usually in combination with one of the previously noted therapeutic modalities. Behavioral modification may also be used in combination with various types of physical therapy or manipulation.