Central neuropathic pain is a common debilitating symptom in patients with multiple sclerosis. Side effects of analgesics often limit reaching therapeutic dosages. In this case report, a 61-year-old woman with chronic central neuropathic pain due to multiple sclerosis is described. Acupuncture could only partly and temporarily reduce the pain. However, after adding the natural compound palmitoylethanolamide, a glial modulator and peroxisome proliferator-activated receptor-α agonist, pain reduction was more pronounced and the interval between acupuncture sessions could be increased. A multimodal stepped care approach is demonstrated, with acupuncture and palmitoylethanolamide both influencing non-neuronal cells, such as activated glial cells, which are key factors in the development and maintenance of neuropathic pain.