Brain, behavior, and immunity · 2026
Multisite chronic pain and incident multiple sclerosis: A prospective cohort study.
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Vazirian Fatemeh, Tian Jing, Alty Jane, Aitken Dawn, Cicuttini Flavia, Jones Graeme, Pan Feng
Аннотация
BACKGROUND: Chronic musculoskeletal pain is common in multiple sclerosis (MS) and pain-inflammation pathways may contribute to neurodegeneration; however, whether chronic pain is associated with later MS remains unclear. This study examined associations between chronic pain and incident MS, and whether inflammation mediates this relationship.
METHODS: Data from 356,010 UK Biobank participants free of MS at baseline were analysed. Chronic pain (≥3 months) in the hip, neck/shoulder, back, knee, or all over the body was documented. Participants were grouped as having no chronic pain, one or two pain sites, three or four sites, and pain all over the body. Incident MS was determined and Cox regression estimated associations between chronic pain and incident MS. Mediation analysis assessed the contribution of systemic inflammation.
RESULTS: Over a median 13-year follow-up, 1,007 participants developed MS. In multivariable analyses, chronic pain was associated with a 26% increased risk of MS compared with those without chronic pain (HR 1.26; 95% CI, 1.10-1.43). A dose-response relationship was observed, with risk increasing by number of pain sites (HR 1.44; 95% CI, 1.32-1.57), and pain all over the body conferred a nearly 4.9-fold higher risk. Partial mediation by inflammation was observed (INFLA-score 1.23%, C-reactive protein 1.77%, white blood cells -0.48%).
CONCLUSION: Chronic musculoskeletal pain was associated with later MS, particularly when involving multiple sites. The association was partly mediated by peripheral inflammation, suggesting that chronic pain may serve as an early marker of MS, and that both conditions may reflect different manifestations of a shared underlying neuroimmune process.
METHODS: Data from 356,010 UK Biobank participants free of MS at baseline were analysed. Chronic pain (≥3 months) in the hip, neck/shoulder, back, knee, or all over the body was documented. Participants were grouped as having no chronic pain, one or two pain sites, three or four sites, and pain all over the body. Incident MS was determined and Cox regression estimated associations between chronic pain and incident MS. Mediation analysis assessed the contribution of systemic inflammation.
RESULTS: Over a median 13-year follow-up, 1,007 participants developed MS. In multivariable analyses, chronic pain was associated with a 26% increased risk of MS compared with those without chronic pain (HR 1.26; 95% CI, 1.10-1.43). A dose-response relationship was observed, with risk increasing by number of pain sites (HR 1.44; 95% CI, 1.32-1.57), and pain all over the body conferred a nearly 4.9-fold higher risk. Partial mediation by inflammation was observed (INFLA-score 1.23%, C-reactive protein 1.77%, white blood cells -0.48%).
CONCLUSION: Chronic musculoskeletal pain was associated with later MS, particularly when involving multiple sites. The association was partly mediated by peripheral inflammation, suggesting that chronic pain may serve as an early marker of MS, and that both conditions may reflect different manifestations of a shared underlying neuroimmune process.