Adrenergic Modulation of Trigeminal Nociceptors

三叉神经伤害感受器的肾上腺素调节

• 批准号: 7115198
• 负责人: JOSE D VELA
• 金额: $ 3.57万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7115198
• 关键词: afferent nerve; beta adrenergic receptor; biological signal transduction; bradykinin; calcitonin gene related peptide; ganglions; genetic regulation; hyperalgesia; laboratory rat; neuropeptide receptor; nociceptors; predoctoral investigator; prostaglandin E; receptor expression; tissue /cell culture; trigeminal nerve

DESCRIPTION (provided by applicant): The beta adrenergic receptors (betaAR) comprise one of the most studied families of G protein coupled receptors (GPCRs), and beta agonists and antagonists are commonly used in clinical pharmacology. Despite this cornucopia of scientific knowledge and clinical experience, comparatively little is know about betaARs and pain. The literature suggests contrasting views on the role of betaARs in pain. In some experimental conditions the activation of the receptor is pronociceptive and under other conditions it is anti-nociceptive leaving the role of the betaARs in pain uncertain. The mechanism of action of the effects of the betaARs on peripheral nociceptors have yet to be fully characterized and this represents an important gap in knowledge. In this application, we propose to test the central hypothesis that beta1 adrenergic receptor activation inhibits trigeminal nociceptors via a direct mechanism of action. Our preliminary results indicate that the mRNA encoding the beta1AR and identified beta1 receptor binding sites are present at greater levels in trigeminal ganglia (TGG) neurons than the beta2 receptor. In addition, application of a beta1 agonist inhibits release of iCGRP when stimulated with BK/PGE2. These preliminary data are consistent with the hypothesis that betaARs agonists inhibit nociceptors via activation of a beta1 adrenergic receptor mechanism.

描述（由申请人提供）：β肾上腺素能受体（betaAR）是研究最多的G蛋白偶联受体（GPCR）家族之一，β激动剂和拮抗剂常用于临床药理学。尽管科学知识和临床经验丰富，但人们对βAR和疼痛的了解却相对较少。文献对 betaAR 在疼痛中的作用提出了不同的看法。在一些实验条件下，受体的激活是促痛性的，而在其他条件下，它是抗痛性的，使得βAR在疼痛中的作用不确定。 betaAR 对外周伤害感受器的作用机制尚未完全确定，这代表了一个重要的知识空白。在本申请中，我们建议测试以下中心假设：β1 肾上腺素能受体激活通过直接作用机制抑制三叉神经伤害感受器。我们的初步结果表明，编码 β1AR 的 mRNA 和已识别的 β1 受体结合位点在三叉神经节 (TGG) 神经元中的存在水平高于 β2 受体。此外，在 BK/PGE2 刺激下，使用 β1 激动剂可抑制 iCGRP 的释放。这些初步数据与 betaAR 激动剂通过激活 β1 肾上腺素能受体机制抑制伤害感受器的假设是一致的。