Multiple sclerosis (MS) represents a major cause of chronic neurological disability in young adults and can result in upper limb sensorimotor impairment with a huge impact on manual dexterity and activities of daily living. Moreover, pain is common in MS and a large proportion of patients suffer from central neuropathic pain. To date, no rehabilitative treatment has been described as useful for these patients. A 46-year-old woman, affected by relapsing-remittent MS, described a one-year history of right shoulder pain (Visual Analogue Scale = 8) that started gradually and without trauma. The patient also presented balance and gait impairments, upper limb strength deficit, and fatigue (Expanded Disability Status Scale = 5.5). A multidisciplinary treatment was proposed, including three intra-articular corticosteroid injections and one month of manual therapy, three sessions/week, based on proprioceptive neuromuscular facilitation for the upper limb. At the end of the rehabilitative treatment, pain relief and an improvement in the range of motion of the affected shoulder, upper limb muscle strength, and hand dexterity were observed. The present paradigmatic case report with literature review demonstrated that a multidisciplinary approach seems to be effective in pain relief in a patient with central neuropathic shoulder pain and relapsing-remitting MS.