Estrogen and Inflammation in TMD Pain

描述（由申请人提供）：关节炎和肌肉骨骼疾病，包括颞下颌关节疾病（TMD），是一种慢性疼痛疾病，在育龄女性中比男性更常见。关节疼痛的神经机制的现状主要依赖于膝关节或踝关节的实验模型。然而，三叉神经和脊柱系统之间的组织差异表明，介导深颅面疼痛的机制不能完全理解从其他模型的关节疼痛获得的结果。所提出的实验使用动物模型来研究在幼稚条件下和慢性炎症期间下三叉神经脑干中的神经元从颞下颌关节（TMJ）发出的伤害性信号。本研究的总体目标是验证性类固醇激素影响TMJ区域感觉信号的中枢神经处理的假设。目的1确定性类固醇替代疗法（雌激素和孕激素）是否可以改变刺激颞下颌关节引起的神经活动。目的2确定性类固醇是否通过谷氨酸受体作用来改变TMJ伤害性信号的处理。目的3确定是否有丝分裂原活化蛋白（MAP）激酶，一个由雌激素和神经生长因子共享的转导途径，有助于处理来自颞下颌关节的伤害性信号。三种方法被用来提供收敛线的证据：c-fos免疫细胞化学确定在单细胞分辨率的神经群体的反应，微透析确定氨基酸递质的释放和电生理记录确定的属性，个别三叉神经元编码的感觉输入从颞下颌关节区域。这些信息可能会导致更好地了解大脑如何整合与女性TMD相关的疼痛样信号

DESCRIPTION (provided by applicant): Arthritis and musculoskeletal disorders, including temporomandibular joint disorders (TMD), are chronic pain conditions that occur more frequently in women of reproductive age than men. Current status of the neural mechanisms of articular pain has relied mainly on experimental models of the knee or ankle joint. However, organizational differences between trigeminal and spinal systems suggest the mechanisms that mediate deep craniofacial pain cannot be fully understood from results obtained by other models of joint pain. The proposed experiments use an animal model to study nociceptive signaling from the temporomandibular joint (TMJ) by neurons in the lower trigeminal brainstem under naive conditions and during chronic inflammation. The overall goal of this study is to test the hypothesis that sex steroid hormones influence central neural processing of sensory signals arising from TMJ region. Aim 1 determines if sex steroid replacement therapy (estrogen and progesterone) modifies neural activity evoked by stimulating the TMJ. Aim 2 determines if sex steroids act through glutamate receptors to modify processing of nociceptive signals from the TMJ. Aim 3 determines if mitogen-activated protein (MAP) kinase, a transduction pathway shared by estrogen and nerve growth factor, contributes to processing of nociceptive signals from the TMJ. Three approaches are used to provide converging lines of evidence: c-fos immunocytochemistry determines neural population responses at single cell resolution, microdialysis determines amino acid transmitter release and electrophysiological recording determines the properties of individual trigeminal neurons that encode sensory input from the TMJ region. This information may lead to a better understanding of how the brain integrates pain-like signals relevant for TMD in women