EFFECT OF INTRATHECAL SEROTONIN ON NOCICEPTION IN RATS - INFLUENCE OFTHE PAIN TEST USED

The involvement of serotonin (5-HT) in the modulation of nociceptive i mpulse in the spinal cord has been widely studied. However, its activi ty, considering the nature of noxious stimuli and the type of 5-HT rec eptors involved, merits to be further elucidated. The present behaviou ral study was performed to compare the dose-antinociceptive effect rel ationship of 5-HT in rats, after intrathecal (i.t.) injection (10 mu l /rat), using mechanical (paw pressure), thermal (tail immersion and ta il-flick) and chemical (formalin) pain tests. In rats submitted to the paw pressure test, 5-HT was found to possess a dose dependent antinoc iceptive activity (0.01, 0.1, 1, 10 and 20 mu g/rat) when vocalization threshold was assessed as a pain parameter. A peak effect occurred 5 min after the injection and the effect was maintained for 45 min. The lowest active dose was 0.1 mu g (maximum increase in vocalization thre sholds, 23 +/- 3%) and a plateau was observed for 10 mu g and 20 mu g (maximum increase in vocalization thresholds, 72 +/- 7% and 71 +/- 6%, respectively). When paw withdrawal was assessed, 5-HT induced a weak hyperalgesic effect for the highest dose (60 mu g), while other doses were ineffective. In the tail-immersion (warmth and cold) and tail-fli ck tests, different doses (0.01, 0.1, 1, 10, 30, 60 and 100 mu g/rat) were studied. In the two immersion tests, only the highest doses (60 m u g and 100 mu g) significantly increased the withdrawal thresholds fr om 5 to 45 min after the injection. The maximum effect was observed at 5 min (23 +/- 4% and 21 +/- 6% for 60 mu g; 27 +/- 3% and 30 +/- 6% f or 100 mu g in the warmth and cold immersion test, respectively). In t he tail-flick test, the doses of 30, 60 and 100 mu g/rat dose-dependen tly and significantly increased the withdrawal thresholds from 5 to 45 min after the injection, with a maximum effect at 5 min (30 +/- 5% fo r 30 mu g; 37 +/- 6% for 60 mu g; and 45 +/- 4% for 100 mu g) In the f ormalin test, 5-HT (10, 25, 50, 75 and 100 mu g/rat) produced dose-rel ated antinociception. The nociceptive response (licking of the injecte d paw) was significantly reduced from 25 mu g (-59 +/- 11%) in the ear ly phase, whereas the lowest active dose in the late phase was 50 mu g (-46 +/- 17%). For both phases, a total inhibition was obtained with 100 mu g. It is concluded that the effect of 5-HT on pain tests may di ffer according to the applied stimulus and the parameter assessed; uns pecific effects of 5-HT may modify motor reactions to noxious stimuli. Mechanical test (assessment of vocalization) was the most sensitive t o 5-HT. These observations are of importance in order to further study the pharmacological mechanisms involved in 5-HT spinally induced anti nociception.