cinanserin and Hyperesthesia

Tryptamine was applied directly into the spinal subarachnoid space of rats via permanently indwelling cannulas. Changes in pain-perception were measured by changes in the latency of the tail-flick in response to a radiant heat source of low intensity. While an intrathecal injection of serotonin has been previously shown to be analgesic, exogenous tryptamine produced dual effects on the pain-threshold, depending on the dose of tryptamine injected. Low doses of tryptamine (100 and 200 micrograms/rat) injected intrathecally onto the sacral area of the spinal cord appeared to be hyperalgesic by significantly decreasing the average tail-flick latency by 5 min after injection. Administration of the serotonin antagonist methysergide alone was without effect on the average tail-flick reaction time when injected either intrathecally or subcutaneously. However, pretreatment with either methysergide or cinanserin not only failed to inhibit tryptamine's potentiation of nociception, but actually enhanced the hyperalgesia produced by tryptamine. In contrast, a dose of 400 micrograms of tryptamine significantly increased the average tail-flick latency, suggesting an analgesic effect at this higher dose. This analgesic effect of 400 micrograms of tryptamine was completely inhibited by subcutaneously administered methysergide, while intrathecally injected methysergide produced even greater decreases in the tail-flick latencies after this high dose of tryptamine. These results suggest that tryptamine, although it differs from serotonin by only one hydroxyl group, may play a role in nociception which is opposite that played by serotonin.

Topics: Animals; Cinanserin; Dose-Response Relationship, Drug; Drug Interactions; Hyperalgesia; Hyperesthesia; Injections, Spinal; Male; Methysergide; Rats; Rats, Inbred Strains; Serotonin; Tryptamines