Figure 3.

Summary of the inferences regarding the contribution of the COMT haplotype, stress, and sex to pain sensitivity. Both the HPS haplotype and stress lead to increased pain sensitivity that is sex-dependent, likely in an epinephrine-mediated manner. In both sexes, COMT-dependent pain responses reach a plateau when stress reaches a certain level, although the plateau occurs at lower levels of stress in females compared to males. One implication is that, if COMT-dependent pain sensitivity is being investigated out of the linear range of the relationship between stress and pain, studies would not properly delineate the extent to which COMT haplotypes contribute to pain perception. The vertical dotted lines represent hypothesized conditions when association results have been assessed in the two cohorts for different stress levels.