Sex differences in Brain Structure in individuals with knee osteoarthritis pain.

There is evidence of sex differences in the prevalence of chronic musculoskeletal pain as well as in experimental pain sensitivity. However, the neurobiological mechanisms contributing to these sex differences are poorly understood, especially with respect to brain structure. The aim of the present study is to examine sex differences in brain structure in persons with knee osteoarthritis (KOA) pain. Participants (mean age=58 years) with KOA pain (n=146, 65% female) completed demographic, self-reported and experimental pain assessments including temporal summation and conditioned pain modulation along with a 3T high-resolution, T1-weighted anatomical scan at 2 study sites in the US. FreeSurfer software (v.7.1.0, http://surfer.nmr.mgh.harvard.edu) was used to examine sex differences in gray matter volume and cortical thickness as well as associations with experimental variables. Maps were set at a vertex-wise threshold of P<0.001, and cluster-level threshold was set at P<0.05, corrected for multiple comparisons, by using Monte Carlo Z simulation and 5000 iterations (Family-Wise-Error, FWE, correction). Controlling for important covariates, men compared to women with KOA had significantly lower cortical thickness in the left anterior insula (p=0.043, FWE corrected two-tailed). Cortical thickness in this region was significantly associated with punctate temporal summation (r=0.325, p=0.024) and endogenous pain inhibition (r=0.558, p=0.011) in men, but not in women (p's>0.05). The results suggest that brain morphological differences between females and men with KOA pain are associated with distinct pain modulatory measures in men, but not in women. Future studies are needed to characterize potential neurobiological mechanisms underlying endogenous pain modulatory capacity across the sexes to further understand the individualized pain experience. R01AG059809, R01AG067757.