Activity changes in rat raphe magnus neurons at different concentrations of fentanyl in vitro.

The nucleus raphe magnus (NRM) is an important descending pain inhibitory system. We postulated that the analgesic action of supraspinally administered opiates results from increased descending inhibitory control of the NRM. We tested whether fentanyl activates NRM neurons in the rat slice preparation using extra-cellular recording. Eighty-seven percent of NRM neurons (total number = 68) tested were spontaneously active with firing frequencies of 0.2-4 spikes/s in artificial cerebrospinal fluid. Application of fentanyl (0.25, 0.5, and 1 mumol/L) increased firing frequencies in 12 of 59 (20%) spontaneously active neurons. In 6 of 9 (67%) silent neurons, fentanyl induced firing activities. Naloxone (1-2 mumol/L) antagonized the increased or induced activities by fentanyl in three neurons. In 13 of 59 (22%) spontaneously active neurons, fentanyl decreased the firing frequencies. Although fentanyl was associated with increased activity in a total of 18 NRM neurons, fentanyl at a higher concentration significantly increased the number of inhibited neurons. The results indicate that fentanyl partly activates the descending inhibitory system originating from the NRM; however, at higher concentrations, it appears also to inhibit this same system.