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Updated: Jan 14, 2026
Author Spotlight: Methodologies and Advancements of Chronic Pain Management Research
Published on: January 5, 2024
The Genetic Association Between Prescription Pain Medication Use and the Risk for Fibromyalgia: A Bidirectional and
Gaojie Zhou1, Wei Cao1, Shuang Liang1
1Department of Anesthesiology, Xiangya Hospital, Central South University, Hunan Province Clinical Research Center for Anesthesia and Perioperative Medicine, Changsha, People's Republic of China.
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.
Insights
Prescription opioid use causally increases fibromyalgia risk. This genetic link persists even after accounting for depression, anxiety, and insomnia, highlighting the need for alternative pain treatments.
Area of Science:
- Genetics
- Pain Medicine
- Pharmacology
Background:
- Growing evidence links prescription opioid use to poor fibromyalgia prognosis.
- The causal relationship between opioid use and fibromyalgia remains unclear.
Purpose of the Study:
- To investigate the causal association between prescription opioid use and fibromyalgia using Mendelian randomization.
- To examine potential mediating roles of major depressive disorder, anxiety disorders, and insomnia.
Main Methods:
- Bidirectional two-sample Mendelian randomization (MR) analysis.
- Multivariable Mendelian randomization (MVMR) to adjust for confounders.
- Mediation MR analysis to assess mediating effects.
Main Results:
- Prescription opioid use showed a causal effect on increasing fibromyalgia risk (IVW OR=1.42, p=3.55E-04; Weighted Median OR=1.40, p=0.01).
- This association remained significant after adjusting for major depressive disorder, anxiety disorders, and insomnia.
- No significant reverse causality from fibromyalgia to opioid use was found, nor associations with non-opioid pain medications.
Conclusions:
- Genetic evidence supports a causal link between prescription opioid use and higher fibromyalgia risk.
- The association is robust against common comorbidities like depression, anxiety, and insomnia.
- Clinicians should consider alternative pain management strategies to mitigate fibromyalgia risk associated with opioid prescriptions.
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