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.

该提议的目的是确定横向的作用 副核（LPBN）介导心血管反应 疼痛。有害刺激通常会引起动脉血液 压力和心率。这些响应是由伤害感受器介导的， 脑干中的心血管中心。最近的解剖学和 电生理研究指向LPBN作为主要投影 来自Lamina I和Lamina II神经元的伤害性输入的位点 脊髓和髓质的脊髓三叉神经核中的髓核。而且 降钙素基因相关肽（CGRP）和P（SP），神经肽 突出参与感官传入和伤害感受途径的是 存在于LPBN中，并与上升的疼痛途径有关。这些 研究将使用单细胞电生理记录技术， 动脉压，心率和交感神经的记录 活性和功能性神经解剖学（C-FOS）确定 LPBN通过刺激介导伤害感受器的压力反应 三叉神经传入系统，该系统在尾部具有离散终止位点 延髓和明确的投影途径通往LPBN。影响 尽管现有数据 在此过程中提出了NTS的次要角色。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和延髓腹侧髓质（RVLM）上确定 施加器响应的髓质交感神经流出站点。这 三叉神经传入系统介导了许多重要的临床疼痛 综合征，包括偏头痛，蛛网膜头痛 出血，三叉神经痛，颞下颌关节疼痛和 角膜和口腔疼痛。因此，更好地理解中心 介导心血管反应的神经机制对有害三叉神经 刺激最终可能会为患者带来新的管理策略 与这些临床综合征。此外，这些发现将做出贡献 对伤害感重之间的中心联系的基本理解 传入信号和心血管调节。