The Genetic Association Between Prescription Pain Medication Use and the Risk for Fibromyalgia: A Bidirectional and Multivariable Mendelian Randomization Analysis.

INTRODUCTION

Increasing evidence has indicated that prescription opioid use is associated with poor prognosis in patients with fibromyalgia. However, it remains unknown whether there are causal associations between prescription opioid and fibromyalgia.

METHODS

We performed a bidirectional two-sample MR analysis using genetic variants associated with prescription pain medication use and fibromyalgia from genome-wide association studies (GWAS). Multivariable Mendelian randomization (MVMR) was further employed to ascertain the causal relationship, incorporating confounders such as major depressive disorder (MDD), anxiety disorders (ADs) and insomnia. A mediation MR analysis was conducted to assess their potential mediating roles.

RESULTS

The forward two-sample Mendelian analysis revealed a positive causal role in the contribution of prescription opioid use to fibromyalgia, as indicated by the Inverse Variance Weighted (IVW) method (OR = 1.42, 95% CI: 1.17, 1.72, p = 3.55E-04) and the Weighted Median method (OR = 1.40, 95% CI: 1.07, 1.83; p = 0.01). In MVMR, the association remained after accounting for MDD, ADs and insomnia, none of which exhibited mediating effects. In the reverse MR analysis, which assessed whether fibromyalgia causally affected prescription opioid use, no significant associations were found. No substantial associations were observed between non-opioid pain medications and fibromyalgia.

CONCLUSION

Our findings provide genetic evidence supporting causal relationship for prescription opioid use on a high risk of fibromyalgia. This association remains robust after adjustment for MDD, ADs and insomnia. Given the potential for opioid prescriptions to increase the risk of developing fibromyalgia, clinicians should prioritize alternative, evidence-based pain management strategies.