Pain Physician. 2025 Nov;28(6):495-510.
ABSTRACT
BACKGROUND: Observational studies have reported relationships among physical activity (PA), leisure sedentary behaviors (LSBs), lifestyle habits, and chronic pain (CP). However, these findings may be unreliable due to confounding biases.
OBJECTIVES: To evaluate the causal effects of PA, LSB, and lifestyle habits on CP.
STUDY DESIGN: This study performed a 2-sample Mendelian randomization to assess the causal effects of the 3 exposures of interest on MCP and evaluated the robustness of the results through a series of sensitivity analyses.
SETTING: The genetic instruments were obtained from UK Biobank, which provides publicly accessible genome-wide association studies (GWAS) summary statistics based on individuals of European ancestry.
METHODS: We used GWAS summary statistics of multisite chronic pain (MCP) in 387,649 individuals from the UK Biobank to identify genetically predicted MCP. Data on PA, LSBs, and lifestyle habits were derived from large GWAS datasets (n > 300,000). Causal effects were assessed by inverse variance weighted (IVW), MR-Egger, weighted median, maximum likelihood, and penalized weighted median. Sensitivity analyses, including MR-PRESSO, Cochran’s Q test, MR-Egger intercept, and leave-one-out analysis, were performed to evaluate the robustness of the MR results.
RESULTS: The results of univariable MR analyses indicated that genetically predicted computer use (OR = 0.905 [0.832, 0.984]) and strenuous sports or other exercises (SSOEs) (OR = 0.490 [0.361, 0.664]) reduced the risk of MCP. Watching television (OR = 1.320 [1.262, 1.380]) and smoking initiation (OR =1.164 [1.122, 1.207]) increased the risk of MCP. Reverse inference results showed that watching television (beta = 0.256 [0.170, 0.341]) and smoking initiation (OR = 1.475 [1.257, 1.732) were risk factors for MCP, while SSOEs (OR = 0.900 [0.871, 0.931) and VPA (OR = 0.945 [0.900, 0.993]) reduced the likelihood of MCP.
LIMITATIONS: This study was unable to use non-overlapping samples to assess the causal association in every 2-sample MR analysis due to the restriction of GWAS datasets, resulting in inevitable bias.
CONCLUSION: This study revealed that television-watching and smoking initiation increased the risk of CP, while computer use and vigorous PA served as protective factors.
PMID:41337762
