BRAIN STEM MECHANISMS MEDIATING THE NOCICEPTIVE PRESSOR RESPONSE

本提案的目标是确定横向 臂旁核（LPBN）介导心血管反应， 痛苦神经刺激通常会刺激动脉血中 血压和心率这些反应是由伤害性和 脑干中的心血管中枢最近的解剖学和 电生理学研究指出LPBN是主要的投射 来自板层I和板层II神经元的伤害性输入的位点 脊髓和三叉神经脊束感觉核。此外 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， 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），以确定的作用， LPBN介导伤害性升压反应的机制 三叉神经传入系统，在尾侧有一个离散的终止点 延髓和明确的投射途径LPBN。的影响 孤束核（NTS）也将进行检查，虽然现有的数据 表明NTS在此过程中起次要作用。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）测定， 延髓交感神经流出部位的升压反应。的 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，蛛网膜炎性头痛 出血，三叉神经痛，颞下颌关节疼痛， 角膜和口腔疼痛。因此，更好地了解中央 三叉神经痛心血管反应的神经机制 刺激可能最终导致新的管理策略，为病人 这些临床症状。此外，这些发现将有助于 对伤害性感受和 传入信号和心血管调节。

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.