Role of purinergic signaling and glia in TMJ nociception

嘌呤能信号和神经胶质细胞在 TMJ 伤害感受中的作用

基本信息

  • 批准号:
    9507148
  • 负责人:
  • 金额:
    $ 47.91万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-08-01 至 2019-07-31
  • 项目状态:
    已结题

项目摘要

Temporomandibular joint disorders (TMD) include a family of conditions that present with pain in the temporomandibular joint (TMJ) and muscles of mastication. TMD is the most common non-dental orofacial pain, yet the underlying physiological and cellular mechanisms are poorly understood. Painful TMD is notable for a higher prevalence in women than men, and poor correlation between overt signs of injury and ratings of pain intensity. Reports of elevated levels of pro-inflammatory molecules in synovial fluid samples of non-osteoarthritic TMD patients suggest that low grade TMJ inflammation is a common feature of TMD, but likely goes undetected without direct synovial fluid sampling. The central hypothesis is that low grade TMJ inflammation primes trigeminal ganglion (TG) neurons and induces persistent hyperalgesia seen as altered response properties of spinomedullary (Vc/C1-2) neurons and jaw muscle activity. We propose that purinergic (P2) receptors and glial cell activation play key roles in TMJ priming and maintain hyperalgesia in a stimulus- and sex-dependent manner. The long-term goal of this project is to determine if interference with specific P2 receptors on neurons and glia are therapeutic targets for managing TMJ nociception and TMD pain in humans. A quantitative sensory testing (QST) protocol is developed to assess treatment effects on TMJ-responsive neurons. Converging lines of evidence using electrophysiological, behavioral, molecular, and anatomical approaches address three issues: 1) is transient low grade TMJ inflammation sufficient to cause persistent changes in the properties of TMJ-responsive TG and Vc/C1-2 neurons, jaw muscle activity and jaw movement; 2) what is the role of purinergic receptors in TMJ priming; and 3) what is the role of glial cells in maintenance of TMJ nociception? Unlike previous studies, this model uses a single exposure to a non-tissue damaging inflammatory agent to prime TMJ-responsive neuronal circuits in male and female rats and couples this insult to the responses of TMJ-responsive neurons with identified phenotypes. Aim 1 establishes the QST protocol under TMJ primed conditions and determines the effects of priming on the properties of TG neurons, Vc/C1-2 neurons, on MMemg activity and jaw movement. Aim 2 determines the expression and protein levels of P2 receptors closely associated with TG and Vc/C1-2 neurons and the role of those receptors on neural activity, jaw muscle activity and jaw movement. Aim 3 determines the expression and protein levels of P2 receptors closely associated with satellite glia in TG and microglia at Vc/C1-2 neurons and the role of glial cell activation in TMJ hyperalgesia. Neuron-glia communication is a critical feature of persistent inflammatory hyperalgesia in other models, but remains poorly defined in TMJ nociception. When coupled with neural recording and jaw muscle reflexes, inhibition of P2 receptors closely associated with neurons or glia, inhibition of inflammasome formation by microglia and blockade of glia-specific secretory products by pharmacological and interference RNA approaches will enhance the understanding of neural mechanisms underlying persistent TMJ hyperalgesia.

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Estrogen Status and Trigeminal Ganglion Responses to Jaw Movement.
雌激素状态和三叉神经节对下颌运动的反应。
  • DOI:
    10.1177/00220345221077951
  • 发表时间:
    2022
  • 期刊:
  • 影响因子:
    7.6
  • 作者:
    Zhang,X;Rahman,M;Bereiter,DA
  • 通讯作者:
    Bereiter,DA
共 1 条
  • 1
前往

DAVID A BEREITER的其他基金

Ocular Hyperalgesia in Dry Eye
干眼症的眼部痛觉过敏
  • 批准号:
    9917769
    9917769
  • 财政年份:
    2017
  • 资助金额:
    $ 47.91万
    $ 47.91万
  • 项目类别:
Ocular Hyperalgesia in Dry Eye
干眼症的眼部痛觉过敏
  • 批准号:
    9364844
    9364844
  • 财政年份:
    2017
  • 资助金额:
    $ 47.91万
    $ 47.91万
  • 项目类别:
Trigeminal-autonomic relations in ocular homeostasis
眼稳态中的三叉神经自主关系
  • 批准号:
    8461195
    8461195
  • 财政年份:
    2011
  • 资助金额:
    $ 47.91万
    $ 47.91万
  • 项目类别:
Trigeminal-autonomic relations in ocular homeostasis
眼稳态中的三叉神经自主关系
  • 批准号:
    8130159
    8130159
  • 财政年份:
    2011
  • 资助金额:
    $ 47.91万
    $ 47.91万
  • 项目类别:
Trigeminal-autonomic relations in ocular homeostasis
眼稳态中的三叉神经自主关系
  • 批准号:
    8240030
    8240030
  • 财政年份:
    2011
  • 资助金额:
    $ 47.91万
    $ 47.91万
  • 项目类别:
Estrogen and Inflammation in TMD Pain
雌激素与 TMD 疼痛中的炎症
  • 批准号:
    7243715
    7243715
  • 财政年份:
    1998
  • 资助金额:
    $ 47.91万
    $ 47.91万
  • 项目类别:
SEX-RELATED OPIATE AND AUTONOMIC MECHANISMS IN TMD PAIN
TMD 疼痛中与性相关的阿片类药物和自主机制
  • 批准号:
    6176887
    6176887
  • 财政年份:
    1998
  • 资助金额:
    $ 47.91万
    $ 47.91万
  • 项目类别:
Estrogen and Inflammation in TMD Pain
雌激素与 TMD 疼痛中的炎症
  • 批准号:
    7082133
    7082133
  • 财政年份:
    1998
  • 资助金额:
    $ 47.91万
    $ 47.91万
  • 项目类别:
SEX-RELATED OPIATE AND AUTONOMIC MECHANISMS IN TMD PAIN
TMD 疼痛中与性相关的阿片类药物和自主机制
  • 批准号:
    2680135
    2680135
  • 财政年份:
    1998
  • 资助金额:
    $ 47.91万
    $ 47.91万
  • 项目类别:
SEX-RELATED OPIATE AND AUTONOMIC MECHANISMS IN TMD PAIN
TMD 疼痛中与性相关的阿片类药物和自主机制
  • 批准号:
    2897219
    2897219
  • 财政年份:
    1998
  • 资助金额:
    $ 47.91万
    $ 47.91万
  • 项目类别:

相似国自然基金

海洋缺氧对持久性有机污染物入海后降解行为的影响
  • 批准号:
    42377396
  • 批准年份:
    2023
  • 资助金额:
    49 万元
  • 项目类别:
    面上项目
氮磷的可获得性对拟柱孢藻水华毒性的影响和调控机制
  • 批准号:
    32371616
  • 批准年份:
    2023
  • 资助金额:
    50 万元
  • 项目类别:
    面上项目
还原条件下铜基催化剂表面供-受电子作用表征及其对CO2电催化反应的影响
  • 批准号:
    22379027
  • 批准年份:
    2023
  • 资助金额:
    50 万元
  • 项目类别:
    面上项目
CCT2分泌与内吞的机制及其对毒性蛋白聚集体传递的影响
  • 批准号:
    32300624
  • 批准年份:
    2023
  • 资助金额:
    10 万元
  • 项目类别:
    青年科学基金项目
在轨扰动影响下空间燃料电池系统的流动沸腾传质机理与抗扰控制研究
  • 批准号:
    52377215
  • 批准年份:
    2023
  • 资助金额:
    50 万元
  • 项目类别:
    面上项目

相似海外基金

Fluency from Flesh to Filament: Collation, Representation, and Analysis of Multi-Scale Neuroimaging data to Characterize and Diagnose Alzheimer's Disease
从肉体到细丝的流畅性:多尺度神经影像数据的整理、表示和分析,以表征和诊断阿尔茨海默病
  • 批准号:
    10462257
    10462257
  • 财政年份:
    2023
  • 资助金额:
    $ 47.91万
    $ 47.91万
  • 项目类别:
Genetics of Extreme Phenotypes of OSA and Associated Upper Airway Anatomy
OSA 极端表型的遗传学及相关上呼吸道解剖学
  • 批准号:
    10555809
    10555809
  • 财政年份:
    2023
  • 资助金额:
    $ 47.91万
    $ 47.91万
  • 项目类别:
Focused ultrasound for memory disorders
聚焦超声治疗记忆障碍
  • 批准号:
    10638189
    10638189
  • 财政年份:
    2023
  • 资助金额:
    $ 47.91万
    $ 47.91万
  • 项目类别:
Designing novel therapeutics for Alzheimer’s disease using structural studies of tau
利用 tau 蛋白结构研究设计治疗阿尔茨海默病的新疗法
  • 批准号:
    10678341
    10678341
  • 财政年份:
    2023
  • 资助金额:
    $ 47.91万
    $ 47.91万
  • 项目类别:
Mechanistic characterization of vaginal microbiome-metabolome associations and metabolite-mediated host inflammation
阴道微生物组-代谢组关联和代谢物介导的宿主炎症的机制特征
  • 批准号:
    10663410
    10663410
  • 财政年份:
    2023
  • 资助金额:
    $ 47.91万
    $ 47.91万
  • 项目类别: