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

Abstract

Stimulation of neurons in the ventromedial medulla produces antinociception in part by inhibiting nociceptive dorsal horn neurons. This antinociceptive effect is mediated in part by spinally projecting noradrenergic neurons located in the A7 catecholamine cell group. Methionine-enkephalin-immunoreactive neurons in the ventromedial medulla project to an area that includes the A7 cell group, and these enkephalin neurons may mediate part of the antinociception produced by stimulation of sites in the ventromedial medulla. This possibility was tested by determining the effects of microinjecting morphine near the A7 cell group on nociceptive foot and tail responses. Microinjection of a 3.75 nmol dose of morphine in the A7 region did not alter nociceptive responses, but a higher dose of 7.5 nmol facilitated these responses. In contrast, a higher dose of 15 nmol of morphine did not alter nociceptive responses. Selective α-adrenoceptor antagonists were injected intrathecally to determine whether the hyperalgesia produced by morphine is mediated by spinally projecting noradrenergic A7 neurons. Intrathecal injection of the α 2-adrenoceptor antagonist yohimbine did not alter the hyperalgesic effect produced by the 7.5 nmol dose of morphine, but the α 1 antagonist WB4101 reversed the hyperalgesia and produced antinociception that lasted for nearly 30 min. Although the 15 nmol dose of morphine did not alter nociceptive responses, intrathecal injection of yohimbine after the microinjection of morphine produced a significant facilitation of nociception, and intrathecal injection of WB401 produced a significant antinociceptive effect. Intrathecal injection of the antagonists alone did not consistently alter nociception. These findings, and those of published reports, suggest that morphine indirectly activates two populations of spinally projecting A7 noradrenergic neurons that have opposing effects on nociception. One of these populations facilitates nociception by an action mediated by α 1-adrenoceptors in the spinal cord dorsal horn and the other population inhibits nociception by an action mediated by α 2-adrenoceptors. These results suggest that some of the methionine-enkephalin neurons located in the ventromedial medulla that project to the A7 cell group can exert bidirectional control of nociceptive responses.