The Causal Relationship Between Chronic Pain and Frailty: A Two-Sample Mendelian Randomization Study.

Objective

Frailty and chronic pain are closely related, but the causal relationship between them needs to be further explored with high-level evidence. Mendelian randomization (MR) was used to analyse the bidirectional causal relationship between nine chronic pain disorders and two frailty indicators in this study.

Methods

We used Causal Analysis Using Summary Effect Estimates (CAUSE) as the primary method of analysis. The inverse-variance-weighted, simple model, weighted model, penalized weighted median and MR‒Egger regression methods were used to evaluate the robustness of the results.

Results

The frailty index (FI) was significantly associated with the number of chronic pain sites (multisite chronic pain, MCP, padjust < .001) and the risk of chronic widespread pain (CWP, padjust < .001). The Fried frailty score (FFS) was significantly associated with MCP (padjust < .001), the risk of CWP (padjust < .001) and chronic back pain (padjust = .031). In the reverse analysis, both MCP and CWP were significantly positively associated with the FI (padjust < .001; padjust = .003) and FFS (padjust < .001; padjust = .009).

Conclusions

This study revealed a bidirectional causal relationship between frailty and chronic pain, with the number of pain sites playing a key role. This finding has significant implications for effectively managing frailty and chronic pain in older adults.