ABSTRACT
Objective The extent to which the association between hypertension and chronic pain in observational studies is either causally linked or influenced by other shared risk factors has not been substantially addressed. In the present study, Mendelian randomization (MR) was employed to examine the potential causal relationship between hypertension and risk of chronic pain. Methods The study data were derived from the pooled dataset of the genome-wide association study (GWAS), enabling the evaluation of the causal effects of hypertension on various types of chronic pain including headache as well as chest, abdominal, joint, back, limb, and multisite chronic pain. We performed a bidirectional two-sample MR analysis using random effect inverse variance weighting (IVW), MR-Egger, and weighted median and weighted mode, quantified by the odds ratio (OR). Results Genetically predicted essential hypertension was associated with an increased risk of chronic headache (OR = 1.007, 95% CI: 1.003-1.011, P = 0.002) and limb pain (OR = 1.219, 95% CI: 1.033-1.439, P = 0.019). No potential causal associations were identified between chronic pain and essential hypertension in the reverse direction MR ( P > 0.05). In addition, there was no potential causal association between secondary hypertension and chronic pain (P > 0.05). Conclusion This study provided genetic evidence that a unidirectional causal relationship exists between essential hypertension and the increased risks of chronic headache and limb pain, and no causal relationship was found between secondary hypertension and chronic pain. These findings offer crucial theoretical underpinnings for future research on managing hypertension and chronic pain.