Microinjection of morphine in the A7 catecholamine cell group produces opposing effects on nociception that are mediated by alpha(1)- and alpha(2)-adrenoceptors

Stimulation of neurons in the ventromedial medulla produces antinociception in part by inhibiting nociceptive dorsal horn neurons. This antinociceptiv e effect is mediated in part by spinally projecting noradrenergic neurons l ocated in the A7 catecholamine cell group. Methionine-enkephalin-immunoreac tive neurons in the ventromedial medulla project to an area that includes t he A7 cell group, and these enkephalin neurons may mediate part of the anti nociception produced by stimulation of sites in the ventromedial medulla. T his possibility was tested by determining the effects of microinjecting mor phine near the A7 cell group on nociceptive foot and tail responses. Microi njection of a 3.75 nmol dose of morphine in the A7 region did not alter noc iceptive responses, but a higher dose of 7.5 nmol facilitated these respons es. In contrast, a higher dose of 15 nmol of morphine did not alter nocicep tive responses. Selective alpha-adrenoceptor antagonists were injected intr athecally to determine whether the hyperalgesia produced by morphine is med iated by spinally projecting noradrenergic A7 neurons. Intrathecal injectio n of the alpha(2)-adrenoceptor antagonist yohimbine did not alter the hyper algesic effect produced by the 7.5 nmol dose of morphine, but the alpha(1) antagonist WB4101 reversed the hyperalgesia and produced antinociception th at lasted for nearly 30 min. Although the 15 nmol dose of morphine did not alter nociceptive responses, intrathecal injection of yohimbine after the m icroinjection of morphine produced a significant facilitation of nociceptio n, and intrathecal injection of WB401 produced a significant antinociceptiv e effect. Intrathecal injection of the antagonists alone did not consistent ly alter nociception. These findings, and those of published reports, suggest that morphine indir ectly activates two populations of spinally projecting A7 noradrenergic neu rons that have opposing effects on nociception. One of these populations fa cilitates nociception by an action mediated by alpha(1)-adrenoceptors in th e spinal cord dorsal horn and the other population inhibits nociception by an action mediated by alpha(2)-adrenoceptors. These results suggest that so me of the methionine-enkephalin neurons located in the ventromedial medulla that project to the A7 cell group can exert bidirectional control of nocic eptive responses. (C) 1999 IBRO. Published by Elsevier Science Ltd.