• Codjo Djignefa Djade, Caroline Diorio, Danielle Laurin, Denis Talbot, Pierre-Hugues Carmichael, and Clermont E Dionne.
• Department of Social and Preventive Medicine, Faculty of Medicine, Université Laval, Québec City, QC, Canada.
• Pain. 2025 Feb 3.

AbstractChronic musculoskeletal pain (CMP) causes significant health loss worldwide and is one of the major public health issues of our time. Cigarette smoking is an independent risk factor of CMP. The present study examined the potential mediating role of 2 subproducts of cigarette smoke, acrylamide and cadmium, individually and combined, on the association between cigarette smoking and CMP, using the Inverse Odds Ratio Weighting (IORW) method. Analyses were conducted on data from 3670 adults who participated to National Health and Nutrition Examination Surveys 2003 to 2004. When smoking was measured with serum cotinine levels, there was an association of moderate and heavy smoking {adjusted Odds Ratio [aOR]>30 ng/mL = 1.99 (95% confidence interval [CI]: 1.44-2.74)} with CMP, but no association between light smoking and CMP (aOR1-30 ng/mL = 1.17 [95% CI: 0.75-1.80]) as compared to nonsmoking. Small indirect effects were identified through acrylamide (aOR = 1.24 [95% CI: 0.96-1.61]) and cadmium (aOR = 1.56 [95% CI: 0.92-2.63]) only among moderate and heavy smokers. When both biomarkers were considered together, their indirect effect was larger (aOR = 2.07 [95% CI: 1.32-3.23]). These results suggest that the association between cigarette smoking and CMP is mediated by acrylamide and cadmium and that these substances, also present in food and the environment, may serve as biomarkers of CMP.Copyright © 2025 International Association for the Study of Pain.

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