Examination of spinal monoamine receptors through which brainstem opiate-sensitive systems act in the rat.

The microinjection through stereotaxically implanted guide cannulae of morphine (5 micrograms/0.5 microliter) into the periaqueductal gray, the n. raphe magnus or the n. reticulogigantocellularis results in a significant elevation in the latency of a thermally evoked, spinally mediated reflex (tail-flick) and a supraspinally organized response (hot-plate). Spinal serotonin, noradrenalin, opiate and dopamine receptors were antagonized by the injection through chronically implanted intrathecal catheters of methysergide, phentolamine, naloxone and cis-flupenthixol, respectively. After a significant elevation of the tail-flick response latencies with intracerebral injections of morphine into the periaqueductal gray, the magnitude of the reversal produced by the intrathecally administered antagonists was phentolamine = methysergide much greater than naloxone = cis-flupenthixol = 0. After a significant elevation of the tail-flick response latency with intracerebral injections of morphine into the n. raphe magnus, the magnitude of the reversal produced by the intrathecally administered antagonist was methysergide greater than phentolamine greater than naloxone much greater than cis-flupenthixol = 0. After a significant elevation of the tail-flick response latency was produced by the microinjection of morphine into the n. reticulogigantocellularis, the magnitude of the reversal produced by intrathecal antagonists was phentolamine greater than naloxone much greater than methysergide = cis-flupenthixol = 0. None of the intrathecal antagonists reversed the elevation of the hot-plate response latencies produced by morphine injections into the n. raphe magnus and n. reticulogigantocellularis injections. A significant, but clearly subtotal reversal of the elevated hot-plate response latencies produced by periaqueductal gray morphine was produced by intrathecal phentolamine and methysergide. It is concluded that discrete populations of brain opiate receptors in the periaqueductal gray, n. raphe magnus and n. reticulogigantocellularis differentially activate spinal monoamine and opioid receptors to modulate thermally evoked spinally mediated reflexes. The general failure of treatments which reverse the segmental reflex inhibition to reverse the hot-plate effects suggests that: other spinopetal pathways are operative; that descending pathways activated by these manipulations do not contribute to the analgesic effects of brainstem morphine; and/or that in addition to spinopetal modulation, brainstem opiate receptors modulate nociceptive transmission at the brainstem level.