Evidence of Sexual Dimorphism in Pain: A Dialogue Between Macrophages and Sensory Neurons via the IL-23/IL-17A/TRPV1 Axis Is a Prevalent Generator of Mechanical Allodynia in Females

Chronic pain is a very disabling disease, which statistically affects women more than men. More and more studies are looking at this sexual difference. In particular, the study by Luo et al., published on September 1, 2021, highlights a particular neuroimmune axis that induces mechanical pain symptoms only in females. In this study, the authors noted that female neuropathic mice secrete more interleukin-23 (IL-23) from their macrophages and that this IL-23 injected into naïve mice causes painful symptoms to mechanical stimuli only in females. The authors identified a pathway from IL-23 to interleukin-17A (IL-17A), which specifically activates C-fibers expressing TRPV1, to induce the expression of mechanical pain symptoms. Finally, the male/female difference could be linked to estrogens and their alpha receptor, expressed in particular by nociceptive fibers and which would act on TRPV1 to participate in the pain phenotype in females.