Pharmacological management of pain in patients with multiple sclerosis

Multiple sclerosis (MS) is an inflammatory, demyelinating, autoimmune disease of the CNS. There are currently a number of disease-modifying medications for MS that modulate or suppress the immune system; however, these medications do not directly relieve MS symptoms, which include visual deficits, gait problems, sensory deficits, weakness, tremor, spasticity and pain, among others. Pain is a common symptom in MS which has recently been estimated to be experienced by more than 40% of patients. Nociceptive pain occurs as an appropriate physiological response transmitted to a conscious level when nociceptors in bone, muscle or any body tissue are activated, warning the organism of tissue damage. Neuropathic pain is initiated as a direct consequence of a lesion or disease affecting the somatosensory system, with no physiological advantage. Nociceptive and neuropathic pain in MS may be present concurrently and at different stages of the disease, and may be associated with other symptoms. Central neuropathic pain has been reported to be among the most common pain syndromes in MS. It is described as constant, often spontaneous, burning occurring more frequently in the lower limbs. Treatment typically includes tricyclic antidepressants and antiepileptic medications, although studies have been conducted in relatively small samples and optimal dosing has not been confirmed. Cannabinoids have been among the few treatments studied in well designed, randomized, placebo-controlled trials for central neuropathic pain. In the largest of these trials, which included 630 subjects, a 15-week comparison between Delta9-tetrahydrocannabinol and placebo was performed. More patients receiving active treatment perceived an improvement in pain than those receiving placebo, although approximately 20% of subjects reported worsening of pain while on active treatment. Trigeminal neuralgia, while affecting less than 5% of patients with MS, is the most studied pain syndrome. The pain can be extreme and is typically treated with carbamazepine, although adverse effects can mimic an MS exacerbation. Painful topic spasms occur in approximately 11% of the MS population and are treated with antispasticity medications such as baclofen and benzodiazepines. Gabapentin has also demonstrated efficacy, but all studies have included small sample sizes. In general, evidence for treating pain in MS is limited. Many clinical features of pain are often unrecognized by clinicians and are difficult for patients to describe. Treatment is often based on anecdotal reports and clinical experience. We present a review of treatment options for pain in MS, which should serve to update current knowledge, highlight shortcomings in clinical research and provide indications towards achieving evidence-based treatment of pain in MS.