Comparison of antinociceptive action of morphine in the periaqueductal gray, medial and paramedial medulla in rat.

Microinjection of morphine (5 micrograms) through stereotaxically implanted microinjection cannulas into the periaqueductal gray (104 sites), medial (n. raphe magnus; 26 sites) and paramedial (n. reticulogigantocellularis; 49 sites) medulla resulted in an increase in the latency of supraspinally (hot-plate) and spinally (tail-flick)-mediated responses evoked by thermal stimuli. This effect of intracerebral morphine on both hot-plate and tail-flick was dose-dependent, and reversed by systemically administered naloxone as well as by naloxone administered by microinjection into the same site. On the basis of frequency of occurrence, time of onset and magnitude of effect of the minimum effective dose, we could demonstrate no difference between the efficacy of morphine acting at sites in the periaqueductal gray, n. raphe magnus or n. reticulogigantocellularis on the supraspinally mediated response. In all areas examined, morphine was able to produce the maximum elevation in response latency. The microinjection of morphine into the periaqueductal gray frequently produced a total block of the thermally evoked spinally mediated tail-flick reflex. Unlike the periaqueductal gray, the systems through which opiates act in the n. raphe magnus or the n. reticulogigantocellularis to suppress spinal reflex activity displayed a clear plateau in their physiological effects. Microinjections of morphine into the n. raphe magnus or n. reticulogigantocellularis never produced a complete block of the spinal reflex. Further increases in inhibition could not be achieved by either a 3-fold increase in dose or bilateral injections into the paramedial medulla. The failure to block spinal reflex activity often occurred at sites where morphine would completely block the hot-plate response. These observations indicate that opiate receptor-linked systems in the mesencephalon and medulla can significantly attenuate the coordinated escape behavior otherwise evoked by a high-intensity thermal stimuli. We find there is no difference in the physiological efficacy of morphine acting in those regions on supraspinally mediated measures of pain responding. The differential effect on spinally mediated reflex function suggests that these several opiate linked systems produce their effect by discriminable mechanisms.