Central afferent pathways conveying nociceptive input to the hypothalamic paraventricular nucleus as revealed by a combination of retrograde labelingand c-fos activation

Previous data have shown that noxious thermal stimulation of the hind leg i n the anesthetized rat causes c-fos activation in the paraventricular nucle us of the hypothalamus (PVN); in other brain nuclei, including the cathecho laminergic cell groups of the caudal medulla; and in the adenohypophysis. S timulation was followed by adrenocorticotropic hormone plasma release but d id not provoke cardiovascular changes. In the current study, the afferent c entral pathways conveying the nociceptive input to the PVN were studied thr oughout the brain by using double labeling for the Fos-protein and the retr ograde tracer cholera toxin subunit B (CTb) injected into the PVN. Although double labeling occurred in several hypothalamic nuclei, the periaqueducta l gray, the lateral parabrachial area, and the catecholaminergic medullary groups, high rates of double labeling occurred only in the cells of the Al region of the ventrolateral medulla (approximate to 83% of CTb-labeled cell s expressing c-fos). Further triple labeling with tyrosine hydroxylase (TH) revealed that >80% of the double-labeled cells were TH-immunoreactive. The spinal cord had the usual strong c-fos expression but showed no retrograde labeling from the PVN. Noxious stimulation caused corticosterone plasma re lease. To ascertain a possible link of spinofugal neurons with the Al cells , biotinylated dextran amine was injected into the spinal dorsal horn. Nume rous anterogradely labeled fibers with bouton-like structures were observed , with the latter apposed to double- and triple-labeled cells in the Al reg ion. It is suggested that a dysynaptic route relayed in the Al region conve ys the nociceptive somatic input from the spinal cord to the PVN. Noxious s timulation may act as a systemic stressor, activating the hypothalamic-pitu itary-adrenal axis. J. Comp. Neurol. 413:129-145, 1999. (C) 1999 Wiley-Liss , Inc.