Pain in Multiple Sclerosis, Is Dimethyl Fumarate Associated to Less Pain, When Compared to Other Disease Modifying Therapies?

Background: Although pain is a common manifestation in patients with multiple sclerosis (MS), previous clinical studies have not explored the possible pharmacological effect of disease modifying therapy (DMT) in pain management. Dimethyl fumarate (DMF) is an oral DMT approved by FDA for treatment of multiple sclerosis. Besides having an anti-inflammatory effect from modulating immune responses, DMF also has the distinct antioxidant effect through the nuclear factor erythroid-2 related factor-2 (Nrf2) - dependent antioxidant response element pathway. According to this unique property, recent animal studies suggest that active metabolite of DMF can inhibit pain behaviors through an inhibition of reactive oxygen species production that involves the central nucleus of amygdala. Therefore, there is a possibility that pain may be less frequent, in MS patients receiving DMF.

Objectives: To compare pain experienced in patients with multiple sclerosis receiving DMF versus other DMT.

Methods: Patients with Relapsing Remitting MS, were invited to participate in the study during their follow up visit at the MS Neurology Clinic at Texas Tech University Health Sciences Center. Participating patients were properly consented.  Pain was assessed by 0-10 numeric rating scale and Short-Form McGill Pain Questionnaire. Electronic medical records were evaluated, current and past DMT was documented.

Results: A total of 96 patients were included. In general, Thirty-nine patients (40.6%) were experiencing severe pain (McGill Pain Questionnaire score ≥ 7). Twenty patients were on DMF, 50.0 % of which were experiencing severe pain. Pain was reported higher in patients who were treated with interferons, in particular Avonex, in which 83.3% of patients were reporting severe pain. No significant difference between other oral medications and DMF was found (P value 0.14). Seventy patients (72.9%) were female. Mean age ± SD was 39.8 ± 10.8 and 44.5 ±12.0 years in DMF and other DMTs group respectively (P value 0.11). The mean duration of disease was 7.0 years in DMF group and 8.2 years in other DMTs group (P value 0.41). The proportion of patients who are currently treated with pain medication was not statistically different between both groups (60.0% in DMF group and 43.4% in other DMTs group, P value 0.19). Pain intensity was 4.8 and 4.8 in DMF and other DMTs groups respectively (P value 0.99). Short-Form McGill Pain Questionnaire score was 5.9 in DMF group and 5.4 in other DMTs group (P value 0.54). The result of our study revealed no statistically significant difference between these two groups with regard to pain.

Conclusions: Pain is common in MS. We were unable to determine, if the use of DMF is associated to less pain. However, Patients on interferons, seemed to be experiencing more pain that the ones on other DMT. Further prospective studies with larger population are necessary for evaluation the association between pain and DMF.