The apparent hyperalgesic effect of a serotonin antagonist in the tail flick test is mainly due to increased tail skin temperature.

It has been suggested that reduced activity in raphe-spinal serotonergic systems induces hyperalgesia. In rats, the serotonin antagonist metergoline (0.5 mg/kg intraperitoneally) reduced tail flick latency by 0.92 sec (p less than 0.001) and increased tail skin temperature by 2.4 degrees C (p less than 0.001) when measured 50 min after injection. Multiple regression analysis with tail flick latency as dependent variable and tail skin temperature and metergoline/vehicle as independent variables revealed a highly significant effect of tail temperature on tail flick latency. The increase of tail skin temperature explained a reduction of tail flick latency of 0.64 of the 0.92 sec observed [B = -0.267 +/- 0.034, t(37)= -7.75, p less than 0.0001]. When the effect on tail skin temperature was taken into account, metergoline reduced tail flick latency by 0.28 sec [B = -0.284 +/- 0.114, t(37) = -2.50, p less than 0.05]. Metergoline (0.5 and 2.0 mg/kg) did not significantly alter plantar paw skin temperature or the response temperature in the increasing temperature hot plate test. Thus, the observed effect of metergoline on tail flick latency is primarily due to an effect on tail skin temperature. The possibility exists that the remaining effect of metergoline may be due to inadequate correction for the skin temperature change, and it is concluded that the study provide no clear evidence for a tonic inhibition of nociception by serotonergic systems.