Sexual dimorphism of neuroimmune interactions in temporomandibular joint disorders pain: contribution of a newly identified female-specific pain signaling axis IL23/IL17A/TRPV1

点击翻译按钮获取中文摘要

Abstract Temporomandibular joint disorders (TMJD) are the most common form of chronic orofacial pain. TMJD affects approximately 10 million Americans and is up to 3 times more prevalent in women than in men. Moreover, clinical studies demonstrated that female TMJD patients exhibit greater pain than males. Unfortunately, precise mechanistic understanding of sexual dimorphism of TMJD pain remains largely unknown, hindering the attempts to develop female-selective pain therapies and improve pain management for female patients. We recently discovered that IL23/IL17A/TRPV1 signaling axis regulates somatosensory mechanical pain via neuro-immune interactions specifically in female naïve mice and in female mice with nerve injuries. At the immune cell level, interleukin 23 (IL23) stimulates the release of interleukin 17A (IL17A) from female, but not male, macrophages. Released IL17A evokes mechanical pain only in female mice via activation of TRPV1- expressing dorsal root ganglion (DRG) sensory neurons. These findings constitute a critical step forward in understanding of sex differences in pain. The overall goal of our parent R01 is to assess the extent to which TRPV1 and TRPA1 in trigeminal ganglion (TG) sensory neurons contribute to TMJD pain. In this exciting Administrative Supplement, we will determine whether this female-specific pain signaling IL23/IL17A/TRPV1 involving macrophage-sensory neuron crosstalk contributes to the sexual dimorphism of TMJD pain, which is mediated by trigeminal sensory system and has its own distinct etiologies. We believe this proposal will significantly complement our goal of the parent R01. More importantly, successfully addressing the proposed studies will greatly enhance our understanding why women are at a greater risk for developing TMJD pain and experience more severe TMJD pain than men, thereby advancing our quest for rationally-targeted new preventions and treatments for TMJD pain in women.