Projections of neurons in the periaqueductal gray to pontine and medullarycatecholamine cell groups involved in the modulation of nociception

Stimulation of neurons in the periaqueductal gray (PAG) produces antinocice ption that is mediated in part by noradrenergic neurons that innervate the spinal cord dorsal horn. Because norepinephrine-containing neurons are not found in the FAG, noncatecholamine neurons in the FAG must project to, and activate, spinally projecting catecholamine neurons located in the pens or medulla. The present studies determined the projections of neurons in the v entrolateral FAG to the A5, A6 (locus coeruleus), and A7 catecholamine cell groups that are known to contain spinally projecting noradrenergic neurons . The anterograde tracer biotinylated dextran amine (BDA) was injected into the ventrolateral FAG, and labeled axon terminal profiles were identified near noradrenergic neurons that were visualized by processing tissue sectio ns for tyrosine hydroxylase immunoreactivity. Highly varicose, anterogradel y labeled terminal profiles were found apposed to the dendrites and somata of tyrosine-hydroxylase-immunoreactive neurons and non-tyrosine-hydroxylase -immunoreactive neurons in the dorsolateral and ventrolateral pontine tegme ntum. These axon terminal profiles were more dense on the side ipsilateral to the BDA deposit, and both A7 and locus coeruleus neurons received a more dense innervation than did the A5 neurons. Although definitive evidence for a direct pathway from FAG neurons to spina lly projecting A7 neurons requires ultrastructural studies, the results of the present studies provide presumptive evidence for direct projections fro m neurons in the FAG to noradrenergic A7 neurons that innervate the spinal cord dorsal horn and modulate pain perception. If neurons in the ventrolate ral FAG do form synapses with noradrenergic A7 neurons, these spinally proj ecting catecholamine neurons may mediate part of the analgesic effect produ ced by systemic administration of morphine. In contrast, the projections of FAG neurons to the A5 cell group and the locus coeruleus may mediate the c ardiovascular and motor effects produced by stimulation of sites in the ven trolateral FAG. (C) 1999 Wiley-Liss, Inc.