This study aimed to compare associations between S1PR modulator use and pain in people with MS (PwMS), with other disease-modifying therapies (DMTs).

Little is known about the impact of DMTs on chronic pain. Preclinical research indicates that the sphingosine-1-phosphate receptor (S1PR) is involved in inflammation and central sensitization. S1PR modulators such as fingolimod can lead to pain relief that extends beyond the effects of immunosuppression.

This is a secondary data analysis that utilized pre-existing items from a prior survey study that examined pain prevalence and phenotypes in 1164 adults with PwMS. Data includes demographics, disability (PDDS), illness duration, DMT use, and pain outcomes. Pain was assessed using validated measures, including PainDETECT, ACR Fibromyalgia Survey Criteria, and PROMIS scales for pain intensity, anxiety, cognition, depression, and sleep disturbances. Pain medication use was also recorded.

A total of 731 participants were included, with 82 receiving an S1PR1 modulator and 649 receiving other DMTs. The S1PR1 group was younger (48 ± 9.9 vs 52.5 ± 12.1; p=0.002), but other clinical characteristics, including sex, race, type of MS, and disability profiles, were similarly distributed between the two groups. After adjusting for age, the frequencies of nociceptive, neuropathic, centralized, and mixed pain were similar in the S1PR and non-S1PR groups. However, those in the S1PR1 group with centralized pain reported lower pain intensity compared to the non-S1PR1 group (48.73 ± 5.2 vs 51.89 ± 5.3; p=0.02). Regarding overlapping chronic conditions, both groups reported similar levels of, anxiety, depression, sleep disturbances, and cognitive function. The use of pain medications was also similar, with NSAIDs, antispasmodics, and anticonvulsants being the most frequently used.

In our cohort of PwMS, S1PR1 modulators demonstrated a benefit in reducing pain intensity in patients suffering from centralized pain compared to other DMTs.