Sex differences in the expression of calcitonin gene-related peptide (CGRP) and its receptor: a review of contradictory and nuanced findings

Women are disproportionately affected by chronic pain, exhibiting greater incidence, severity, and duration of pain across a wide range of conditions. Women with chronic pain are also more likely to develop comorbid affective disorders, such as depression and anxiety. Although societal and environmental factors contribute to this sex bias, biological factors are also thought to play a role in these sex differences. One biological factor is calcitonin gene-related peptide (CGRP), a neuropeptide with established roles in the pathogenesis of several chronic pain conditions, including migraine. A prevailing hypothesis is that differences in the expression of CGRP and its receptor are involved in sex differences in chronic pain. We explore the evidence for this by reviewing the literature. We find that only a few studies, typically with small sample sizes, address this hypothesis. In aggregate, these studies provide nuanced and contradictory evidence for sex differences in the expression of CGRP and its receptor. However, we present published data that support the conclusion that the CGRP pathway functions differently in males and females.