Pain in multiple sclerosis: clinical phenotypes and therapeutic strategies - a narrative review.

INTRODUCTION

Pain is a frequent and burdensome symptom in multiple sclerosis (MS), yet it remains underrecognized and undertreated.

OBJECTIVE

This review summarizes current knowledge on the prevalence, mechanisms, clinical phenotypes, and therapeutic strategies of MS-related pain, with an emphasis on implications for clinical management.

METHODS

We conducted a narrative review of the literature, integrating epidemiological, clinical, and mechanistic evidence on pain in MS.

RESULTS

Pain is reported by 29% to 86% of people with MS, and up to one-third describe it as their most distressing symptom. Multiple sclerosis-related pain can be classified mechanistically as nociceptive, neuropathic, nociplastic, or mixed. Common clinical syndromes include migraine, tension-type headache, optic neuritis-related pain, trigeminal neuralgia, painful spasticity, and Lhermitte sign. Nociplastic, fibromyalgia-like widespread pain has recently gained attention but remains poorly defined. Evidence for pharmacological interventions - such as anticonvulsants, tricyclic antidepressants, muscle relaxants, corticosteroids for acute optic neuritis, and nabiximols for spasticity - is limited, with few trials addressing specific pain subtypes. Among nonpharmacological strategies, structured exercise shows the most consistent benefits for MS-related pain, whereas evidence for other approaches, including physiotherapy, psychological interventions, and neuromodulation, remains limited. Nevertheless, multimodal strategies addressing co-occurring fatigue, depression, and sleep disturbance appear most effective.

CONCLUSION

Pain is common and disabling across all MS phenotypes but is often insufficiently addressed in clinical practice. A mechanism-based classification combined with individualized, multimodal treatment offers the most promising framework to improve patient outcomes.