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。目前对关节疼痛的神经机制的研究主要依赖于膝关节或踝关节的实验模型。然而，三叉神经系统和脊柱系统之间的组织差异表明，通过其他关节疼痛模型获得的结果无法完全理解介导深部颅面疼痛的机制。本实验采用动物模型研究在初始条件和慢性炎症条件下，三叉神经下部脑干神经元从颞下颌关节（TMJ）发出的伤害性信号。本研究的总体目的是验证性类固醇激素影响中枢神经处理颞下颌关节区产生的感觉信号的假设。目的1确定性类固醇替代疗法（雌激素和黄体酮）是否会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改变颞下颌关节的伤害性信号处理。目的3确定丝裂原活化蛋白激酶（MAP）是否参与颞下颌关节痛觉信号的加工，这是雌激素和神经生长因子共享的转导途径。三种方法用于提供趋同的证据线：c-fos免疫细胞化学确定单细胞分辨率下的神经群体反应，微透析确定氨基酸递质释放，电生理记录确定编码TMJ区感觉输入的单个三叉神经元的特性。这一信息可能会让我们更好地理解大脑是如何整合与女性TMD相关的疼痛信号的

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