Evidence that disinhibition of brain stem neurones contributes to morphine analgesia

Abstract

Analgesia results when opiates are microinjected into the rostral ventromedial medulla (RVM)^1–3. This region, which includes the nucleus raphe magnus and the adjacent reticular formation, is rich in immunoreactive enkephalin-containing neurones and terminals⁴, and contains neurones that project to the spinal cord dorsal horn where they inhibit identified nociceptive spinothalamic tract neurones^5–7. Although opiates have previously been reported either to excite or inhibit RVM cells⁸, the possibility of an opiate effect being consistent within a physiologically defined subclass has not been examined. Recently we described a class of neurone in the RVM (the off-cell) that abruptly pauses just before a heat-evoked tail-flick reflex⁹. If off-cells are made to fire continuously by direct electrical stimulation of the RVM, the tail-flick reflex does not occur. We report here that analgesic doses of morphine completely eliminate the pause in firing that precedes the tail-flick reflex. We propose that this disinhibition of off-cells in the RVM is a primary process contributing to opiate inhibition of nociceptor-induced reflexes.