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.
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