Unravelling the spine-gut–pain connection: chronic musculoskeletal pain and digestive dysfunction in a large-scale population-based cohort of 110,685 individuals

Purpose: To evaluate the association between chronic musculoskeletal pain (CMP) and constipation, and to determine whether the association is mediated or moderated by physical activity, pain medications, or diet. Methods: Cross-sectional data from the UK Biobank (2006–2010) were analyzed, with constipation defined by the ROME-IV criteria as outcome. Generalized linear models assessed associations between CMP and constipation. Causal mediation and moderation analyses examined the roles of physical activity, pain medications (opioids, NSAIDs), and diet. Results: Among 110,685 participants, 36,586 reported CMP. Chronic back pain (odds ratio [OR]: 1.31, 95% confidence interval [CI]: 1.23–1.38), neck/shoulder pain (OR: 1.26, 95%CI: 1.18–1.34), hip pain (OR: 1.14, 95%CI: 1.04–1.25), and knee pain (OR: 1.11, 95%CI: 1.05–1.17) were significantly associated with higher constipation prevalence compared to asymptomatic individuals (P < 0.01). A dose-response was observed for multisite pain (ORs for 1, 2, 3, and 4 sites: 1.20, 1.40, 1.69, and 2.06, respectively; p < 0.001). NSAID use mediated associations for all CMP types, while both opioids and NSAIDs mediated effects for multisite pain. Notably, higher physical activity attenuated the association between constipation and having 2 painful sites. Conclusion: CMP is significantly associated with constipation, mediated by pain medication, and moderated by physical activity. These findings highlight the need for comprehensive digestive health management in adults with CMP, especially those with chronic back pain and multisite pain. Future mechanistic studies should investigate the association between gut dysbiosis and CMP, as well as the roles of physical activity in moderating the relationship between constipation and CMP.