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

颞下颌关节疾病疼痛中神经免疫相互作用的性别二态性：新发现的女性特异性疼痛信号轴 IL23/IL17A/TRPV1 的贡献

基本信息

批准号：
10596384
负责人：
Yong Chen
金额：
$ 12.8万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2024-06-30
项目状态：
已结题

项目摘要

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.

摘要颞下颌关节紊乱病（TMJD）是最常见的慢性口面疼痛。TMJD影响大约有1000万美国人，女性的患病率是男性的3倍。此外，委员会认为，临床研究表明女性TMJD患者比男性表现出更大的疼痛。不幸的是，精确对TMJD疼痛的性二态性的机械理解在很大程度上仍然未知，阻碍了对TMJD疼痛的研究。尝试开发女性选择性疼痛疗法并改善女性患者的疼痛管理。我们最近发现，IL 23/IL 17 A/TRPV 1信号轴通过调节躯体感觉机械性疼痛，神经免疫相互作用，特别是在雌性幼稚小鼠和神经损伤的雌性小鼠中。在在免疫细胞水平，白细胞介素23（IL 23）刺激雌性白细胞介素17 A（IL 17 A）的释放，但不刺激雌性白细胞介素17 A（IL 17 A）的释放。雄性巨噬细胞释放的IL 17 A仅在雌性小鼠中通过激活TRPV 1引起机械性疼痛。表达背根神经节（DRG）感觉神经元。这些研究结果是向前迈出的关键一步，了解疼痛的性别差异。我们的父R 01的总体目标是评估三叉神经节（TG）感觉神经元中的TRPV 1和TRPA 1参与TMJD疼痛。在这个激动人心管理补充，我们将确定是否这种女性特异性疼痛信号IL 23/IL 17 A/TRPV 1 涉及巨噬细胞-感觉神经元的串扰有助于TMJD疼痛的性二态性，它由三叉神经感觉系统介导，有其独特的病因。我们认为，这项建议将这对我们的R 01目标有很大的补充作用。更重要的是，成功解决拟议的问题研究将大大提高我们对为什么女性患TMJD疼痛的风险更大的理解，经历比男性更严重的TMJD疼痛，从而推进我们对合理靶向新疗法的追求。预防和治疗女性TMJD疼痛。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Sensory Neuron-TRPV4 Modulates Temporomandibular Disorder Pain Via CGRP in Mice.

DOI：
10.1016/j.jpain.2022.12.001
发表时间：
2022-12
期刊：
The journal of pain
影响因子：
0
作者：
A. Suttle;Peng Wang;Fabiana C. Dias;Qiaojuan Zhang;Yuhui Luo;Lauren Simmons;A. Bortsov;I. Tchivileva;A. Nackley;Yong Chen
通讯作者：
A. Suttle;Peng Wang;Fabiana C. Dias;Qiaojuan Zhang;Yuhui Luo;Lauren Simmons;A. Bortsov;I. Tchivileva;A. Nackley;Yong Chen

Silencing of TRPV4-expressing sensory neurons attenuates temporomandibular disorders pain.