Intrathecal coadministration of serotonin and morphine differentially modulates the tail-flick reflex of intact and...

In a previous study, we found that the antinociceptive effect of IT-administered morphine on the tail-flick (TF) reflex of rats was potentiated within 1 day after spinal transection. This suggested that the analgesic effect of spinal morphine in the intact animal was tonically suppressed, presumably by the release of a transmitter(s) from descending supraspinal pathway(s), and that the potency of IT morphine was increased because these inputs were removed by spinalization. Because spinally projecting serotonin [5-hydroxytryptamine (5-HT)] fibers are known to be involved in modulating nociception at this site, the present studies examined the possibility that 5-HT might be the proposed "antiopiate" at the spinal cord. Separate groups of intact and spinal rats were pretested on the TF and then injected IT with either morphine (intact: 0.25-5.0 micrograms, spinal: 0.0312-0.5 microgram) or 5-HT (1-200 micrograms), or combinations of these two agents, in a single solution. All rats were then retested 15 min later and the difference in latency was used to compare the effect of these treatments. The results confirmed that the antinociceptive effect of IT morphine was significantly increased by spinalization, whereas the antinociceptive effect of 5-HT was essentially abolished. In intact rats, morphine-induced analgesia was potentiated by a low (10 micrograms) dose of 5-HT but not by higher doses. However, in the spinal rat morphine-induced antinociception was antagonized by the same (10 micrograms) dose. The data suggest that IT 5-HT promotes antinociception in intact rats but acts pro-nociceptively in spinal rats.(ABSTRACT TRUNCATED AT 250 WORDS)