BRAIN STEM MECHANISMS MEDIATING THE NOCICEPTIVE PRESSOR RESPONSE

调节伤害性压力反应的脑干机制

• 批准号: 6564792
• 负责人: Robert B Felder
• 金额: $ 23.33万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6564792
• 关键词: afferent nerve; baroreceptors; brain stem; calcitonin gene related peptide; central neural pathway /tract; electrophysiology; hemodynamics; hypertension; immunocytochemistry; laboratory rat; neural information processing; neuropeptides; neuroregulation; pain; parabrachial nucleus; sensory receptors; single cell analysis; solitary tract nucleus; substance P; trigeminal nerve; vasoconstrictors; voltage /patch clamp

The goal of this proposal is to determine the role of the lateral parabrachial nucleus (LPBN) in mediating the cardiovascular responses to pain. Noxious stimulation typically elicits increases in arterial blood pressure and heart rate. These responses are mediated by nociceptive and cardiovascular centers in the brain stem. Recent anatomical and electrophysiological studies point to the LPBN as the major projection site for nociceptive inputs from lamina I and lamina II neurons in the spinal cord and the spinal trigeminal sensory nucleus in medulla. Moreover calcitonin gene-related peptide (CGRP) and substance P (SP), neuropeptides prominently involved in sensory afferent and nociceptive pathways, are present in LPBN and have been implicated in ascending pain pathways. These studies will use single cell electrophysiological recording techniques, recordings of arterial pressure, heart rate and sympathetic nerve activity, and functional neuroanatomy (c-fos) to determine the role of the LPBN in mediating the nociceptive pressor response by stimulating the trigeminal afferent system which has a discrete termination site in caudal medulla and well defined projection pathways to LPBN. The influence of the solitary tract nucleus (NTS) will also be examined, though existing data suggest a secondary role for NTS in this process. Finally, the interactions of baroreceptor afferent signals with noxious inputs will be determined at LPBN and at the rostral ventrolateral medulla (RVLM), the medullary sympathetic outflow site for the pressor response. The trigeminal afferent system mediates a number of important clinical pain syndromes, including migraine headache, the headache of arachnoid hemorrhage, trigeminal neuralgia, temporal mandibular joint pain and corneal and oral cavity pain. Thus, a better understanding of the central neural mechanisms mediating cardiovascular responses to noxious trigeminal stimulation may ultimately lead to new management strategies for patients with these clinical syndromes. In addition, these findings will contribute to the basic understanding of the central link between nociceptive afferent signals and cardiovascular regulation.

该提案的目标是确定横向的作用 臂旁核（LPBN）介导心血管反应 疼痛。有害刺激通常会引起动脉血增加 压力和心率。这些反应是由伤害性和 心血管中枢位于脑干。最近的解剖学和 电生理学研究指出 LPBN 是主要预测 来自第一层和第二层神经元的伤害性输入的位点 脊髓和髓质内的脊髓三叉神经感觉核。而且 降钙素基因相关肽（CGRP）和P物质（SP）、神经肽 主要参与感觉传入和伤害性通路的是 存在于 LPBN 中并与上行疼痛通路有关。这些 研究将使用单细胞电生理记录技术， 记录动脉压、心率和交感神经 活动和功能神经解剖学（c-fos）以确定 LPBN 通过刺激 三叉神经传入系统，在尾侧有一个离散的终止位点 髓质和明确的 LPBN 投射路径。的影响 孤束核（NTS）也将被检查，尽管现有数据 建议 NTS 在此过程中发挥次要作用。最后， 压力感受器传入信号与有害输入的相互作用将是 在 LPBN 和延髓头端腹外侧 (RVLM) 处确定， 延髓交感神经升压反应的流出部位。这 三叉神经传入系统介导许多重要的临床疼痛 综合征，包括偏头痛、蛛网膜样头痛 出血、三叉神经痛、颞下颌关节痛等 角膜和口腔疼痛。从而更好地了解中央 介导心血管对有害三叉神经反应的神经机制 刺激可能最终为患者带来新的管理策略 患有这些临床综合症。此外，这些发现将有助于 对伤害感受之间的中心联系有基本的了解 传入信号和心血管调节。