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

Area of Science:

• Gerontology
• Pain Medicine
• Genetic Epidemiology

Background:

• Frailty and chronic pain are prevalent conditions in older adults, often co-occurring.
• The precise causal relationship between frailty and chronic pain requires further investigation with robust evidence.

Purpose of the Study:

• To investigate the bidirectional causal relationship between nine chronic pain disorders and two frailty indicators using Mendelian randomization.
• To elucidate the role of pain site count in the frailty-chronic pain association.

Main Methods:

• Mendelian randomization analysis employing the Causal Analysis Using Summary Effect Estimates (CAUSE) method.
• Robustness checks using inverse-variance-weighted, simple model, weighted model, penalized weighted median, and MR-Egger regression.

Main Results:

• The frailty index (FI) and Fried frailty score (FFS) were significantly associated with multisite chronic pain (MCP) and chronic widespread pain (CWP).
• FFS also showed a significant association with chronic back pain.
• Reverse analysis confirmed significant positive associations of MCP and CWP with both FI and FFS.

Conclusions:

• A bidirectional causal relationship exists between frailty and chronic pain.
• The number of chronic pain sites is a critical mediator in this relationship.
• Findings offer insights for managing frailty and chronic pain in the elderly population.