权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Sex Steroids, and TMJ Pain

性类固醇和颞下颌关节疼痛

基本信息

批准号：
7840876
负责人：
LARRY L BELLINGER
金额：
$ 1.32万
依托单位：
TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-02 至 2010-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7840876
关键词：
Acute Acute Pain Address Affect Animals Arthralgia Attenuated Behavioral Biological Models Calcitonin Gene-Related Peptide Candidate Disease Gene Data Diagnosis Disease Dose Eating Endocrine Environment Enzyme-Linked Immunosorbent Assay Estradiol Estrogens Evaluation Feeding behaviors Female Freund&apos s Adjuvant Future Gender Gene Expression Genes Goals Gonadal Steroid Hormones Hormonal Hormone Receptor Hormones Human Development Intervention Joints Laboratories Lead Measures Mechanics Methods Modeling Molecular Nociception Oral Surgeon Pain Pathway interactions Pattern Peripheral Pharmacologic Substance Physiological Plasma Procedures Proestrus Progesterone Proteins Rattus Research Research Personnel Role Sex Characteristics Signal Transduction Sprague-Dawley Rats Structure of trigeminal ganglion Substance P Techniques Temporomandibular Joint Temporomandibular Joint Disorders Testing Testosterone Time Tissues Transcript Work Working Women allodynia arthropathies base behavior measurement computerized experience gene function human subject innovation male novel programs time use working men

项目摘要

DESCRIPTION: The long term goal of this study is to determine the impact of gender differences and sex hormones on gene(s) and molecular pathways leading to and effecting acute and persistent joint pain as observed in the temporomandibular joint (TMJ) and associated peripheral tissues. The objective of this application is to determine the peripheral effect that steroid sex hormones have on acute pain and identify nociception gene(s) that function in pain pathways as modeled in the TMJ. Our central hypothesis is that changes in physiological estrogen, progesterone and testosterone concentrations modulates acute pain as modeled in the TMJ through action at peripheral tissue(s) within and surrounding the joint and/or within the trigeminal ganglia. To test our central hypothesis and attain the objective of this application we propose the following two Specific Aims first, we will characterize pain in the TMJ and surrounding region related to endogenous and administered estrogen and progesterone in females. Second, we will characterize gender differences in pain in the TMJ and surrounding region by determining the modulatory effect of sex steroids in males. The working hypothesis for Specific Aim one is that cyclical plasma levels of estrogen and/or progesterone in females modulates TMJ pain, in part, through changes in gene expression in the joint and/or trigeminal ganglia. To test the working hypothesis the experimental approach will consist of injecting complete Freund's adjuvant (CFA) into the superior TMJ space. The ovariectomized Sprague-Dawley rats will have been treated with physiological doses of 17-beta estradiol and/or progesterone with and without hormone receptor antagonists. The rats will be first tested for TMJ pain using an established non-invasive behavioral procedure. This test uses the time required to eat a meal (i.e., meal duration), as a behavioral measure of pain. Second, changes in the transcript levels of nearly four thousand genes will be measured in the TMJ and trigeminal ganglia of these treated animals with gene microarrays. Third, candidate gene(s) from the gene array studies that were 1) modulated by hormonal treatment and 2) function in pain related pathways will be further quantitated by real-time PCR, ELISA and/or westerns to measure transcript and protein levels. The working hypothesis for Specific Aim two is that low non-cyclical plasma levels of estrogen and/or high testosterone in the males modulates pain through changes in gene expression in the joint and/or trigeminal ganglia. To test the working hypothesis the experimental approach will consist of measuring pain (i.e., meal duration) on castrated and intact male rats treated with and without estrogen before and after injecting CFA in the TMJ. Upon sacrifice transcript levels will be measured. We expect these data will be used for the evaluation and treatment of gender-related TMJ disorders and for mechanistic studies into hormonal action on joint pain. The rationale for completing these proposed studies is that once the hormones influencing pain sensitivity have been characterized and the gene(s) modulated by these hormonal effects in the joint and trigeminal ganglion identified, targets for pharmaceutical intervention of pain in the TMJ can be pursued.

产品说明：本研究的长期目标是确定性别差异和性激素对导致和影响颞下颌关节（TMJ）和相关外周组织中观察到的急性和持续性关节疼痛的基因和分子途径的影响。本申请的目的是确定类固醇性激素对急性疼痛的外周效应，并鉴定在TMJ中模拟的疼痛通路中起作用的伤害感受基因。我们的中心假设是生理雌激素、孕酮和睾酮浓度的变化通过作用于关节内和周围和/或三叉神经节内的外周组织来调节TMJ中模拟的急性疼痛。为了检验我们的中心假设并达到本申请的目的，我们首先提出以下两个具体目标，我们将表征与女性内源性和施用的雌激素和孕激素相关的TMJ和周围区域的疼痛。其次，我们将通过确定男性性类固醇的调节作用来表征颞下颌关节及周围区域疼痛的性别差异。具体目标一的工作假设是，女性的雌激素和/或孕激素的周期性血浆水平调节TMJ疼痛，部分是通过改变关节和/或三叉神经节中的基因表达。为了测试工作假设，实验方法将包括将完全弗氏佐剂（CFA）注射到上级TMJ空间中。卵巢切除的Sprague-Dawley大鼠将用生理剂量的17-β雌二醇和/或孕酮处理，有或没有激素受体拮抗剂。将首先使用已建立的非侵入性行为程序测试大鼠的TMJ疼痛。该测试使用吃饭所需的时间（即，饮食持续时间），作为疼痛的行为测量。第二，将用基因微阵列在这些治疗动物的颞下颌关节和三叉神经节中测量近4000个基因的转录水平的变化。第三，将通过实时PCR、ELISA和/或蛋白质印迹法进一步定量来自基因阵列研究的候选基因，所述候选基因1）受激素治疗调节和2）在疼痛相关途径中的功能，以测量转录物和蛋白质水平。具体目标2的工作假设是，雄性动物中雌激素的低非周期性血浆水平和/或高睾酮水平通过关节和/或三叉神经节中基因表达的变化调节疼痛。为了测试工作假设，实验方法将包括测量疼痛（即，在TMJ中注射CFA之前和之后，对用和不用雌激素处理的去势和完整雄性大鼠进行观察。处死后，将测量转录水平。我们希望这些数据将用于评估和治疗性别相关的颞下颌关节疾病和机制的研究激素对关节疼痛的作用。完成这些拟议研究的基本原理是，一旦表征了影响疼痛敏感性的激素，并确定了关节和三叉神经节中受这些激素作用调节的基因，就可以追求TMJ疼痛药物干预的目标。