The antinociception produced by microinjection of a cholinergic agonist inthe ventromedial medulla is mediated by noradrenergic neurons in the A7 catecholamine cell group

Activation of neurons in the ventromedial medulla by electrical stimulation or by microinjection of opioid or cholinergic agonists produces antinocice ption that is mediated in part by spinally-projecting noradrenergic neurons . Several Lines of evidence indicate that these noradrenergic neurons are l ocated in the pontine A7 catecholamine cell group. For example, anatomical studies have demonstrated that neurons in the ventromedial medulla project to the noradrenergic neurons in the A7 catecholamine cell group that provid e the major noradrenergic innervation of the spinal cord dorsal hem. In add ition, electrical and chemical stimulation of A7 neurons produces antinocic eption that can be reduced by intrathecal injection of alpha(2)-adrenocepto r antagonists. The present studies provide more direct evidence that activa tion of neurons in the ventromedial medulla produces antinociception by act ivating noradrenergic neurons in the A7 cell group. Neurons in the ventrome dial medulla were stimulated by microinjecting the cholinergic agonist carb achol (5 mu g) into sites in the nucleus raphe magnus or the nucleus gigant ocellularis pars alpha of pentobarbital anesthetized Sprague-Dawley rats. I n some experiments, the local anesthetic tetracaine (10 mu g) was then micr oinjected near the A7 cell group to inactivate the spinally-projecting nora drenergic neurons. In other experiments, cobalt chloride (100 mM) was micro injected near the A7 cell group to block synaptic activation of spinally-pr ojecting noradrenergic neurons. Microinjection of carbachol into sites in t he ventromedial medulla produced antinociception, assessed using the tail f lick test, that lasted more than 60 min. However, the effects of carbachol were attenuated by microinjection of either tetracaine or cobalt into sites near the A7 cell group neurons identified by tyrosine hydroxylase-immunore activity. Similar injections of tetracaine or cobalt more than 500 mu m fro m the A7 neurons did not alter the antinociceptive effect of carbachol. The se results support the conclusion that the antinociception produced by acti vating neurons in the ventromedial medulla is mediated in part by the subse quent activation of spinally-projecting noradrenergic neurons in the A7 cel l group. (C) 1999 Elsevier Science B.V. All rights reserved.