Mendelian randomization study: The association between pain, analgesics, and frailty.

Pain, frailty, and the use of analgesic medications often occur together. Previous studies have demonstrated a strong link between them. The purpose of this study was to investigate the causal effects of pain and analgesic medication on frailty. This bidirectional two-sample Mendelian randomization study included summary statistics of pain at different sites (headache, neck or shoulder pain, stomach or abdominal pain, hip pain, back pain, and knee pain), analgesics (aspirin, ibuprofen, paracetamol, and morphine), and frailty index. Mendelian randomization results were primarily interpreted using the inverse-variance weighted method. The false discovery rate was used to correct the P-values of multiple tests. We discovered suggestive evidence for two-way causal relationships between genetically predicted headache, neck or shoulder pain, stomach or abdominal pain, hip pain, back pain, knee pain, and increased frailty index. Suggestive evidence indicated that genetically predicted use of aspirin, ibuprofen, and paracetamol was associated with an increased frailty index risk. Morphine use showed no significant effect. A higher frailty index resulted in an increase in the frequency of using aspirin and paracetamol. Our study provides suggestive evidence for causal links between frailty and multisite pain. Findings suggest that common analgesic use (aspirin, ibuprofen, and paracetamol) may contribute to frailty risk, while frailty increases analgesic use. Results do not support using analgesic-based pain management for frailty improvement.