C-Reactive Protein (CRP) is Associated With Chronic Pain Independently of Biopsychosocial Factors

Inflammation is linked with chronic pain but the extent to which this relationship is associated with biopsychosocial factors is not known. We investigated relationships between blood C-reactive protein (CRP) and regional chronic pain conditions adjusting for a large range and number of potential confounders. We performed cross-sectional analyses using the UK Biobank (N = 415,567) comparing CRP in people reporting any of 9 types of regional chronic pain with pain-free controls. Using logistic regression modelling, we explored relationships between CRP and the presence of chronic pain, with demographic, socioeconomic, psychological/lifestyle factors, and medical comorbidities as covariates. CRP was higher in chronic pain at any site compared with controls (Females: median [interquartile range] 1.60 mg/L [2.74] vs 1.17 mg/L [1.87], P < .001; Males: 1.44 mg/L [2.12] vs 1.15 mg/L [1.65], P < .001). In males, associations between CRP and all types of chronic pain were attenuated but remained significant after adjustment for biopsychosocial covariates (OR range 1.08–1.49, P ≤ .001). For females, adjusted associations between CRP and pain remained significant for most chronic pain types (OR range 1.07–1.34, P < .001) except for facial pain (OR 1.04, P = .17) and headache (OR 1.02, P = .07)—although these non-significant findings may reflect reduced sample size. The significant association between CRP and chronic pain after adjustment for key biopsychosocial confounders implicates an independent underlying biological mechanism of inflammation in chronic pain. The presence of yet unknown or unmeasured confounding factors cannot be ruled out. Our findings may inform better-targeted treatments for chronic pain. Perspective Using a large-scale dataset, this article investigates associations between chronic pain conditions and blood C-reactive protein (CRP), to evaluate the confounding effects of a range of biopsychosocial factors. CRP levels were higher in those with chronic pain versus controls after adjusting for confounders—suggesting a possible independent biological mechanism.