Effect of intrathecal serotonin on nociception in rats: influence of the pain test used

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Abstract
The involvement of serotonin (5-HT) in the modulation of nociceptive impulse in the spinal cord has been widely studied. However, its activity, considering the nature of noxious stimuli and the type of 5-HT receptors involved, merits to be further elucidated. The present behavioural study was performed to compare the doseantinociceptive effect relationship of 5-HT in rats, after intrathecal, (i.t.) injection (10 μl/rat), using mechanical (paw pressure), thermal (tail immersion and tail-flick) and chemical (formalin) pain tests. In rats submitted to the paw pressure test, 5-HT was found to possess a dose-dependent antinociceptive activity (0.01, 0.1, 1, 10 and 20 μg/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 μg (maximum increase in vocalization thresholds, 23±3%) and a plateau was observed for 10 μg and 20 μg (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 (60μg), while other doses were ineffective. In the tail-immersion (warmth and cold) and tail-flick tests, different doses (0.01, 0.1, 1, 10, 30, 60 and 100 μg/rat), were studied. In the two immersion tests, only the highest doses (60 μg and 100 μg) significantly increased the withdrawal thresholds from 5 to 45 min after the injection. The maximum effect was observed at 5 min (23±4% and 21±6% for 60 μg; 27±3%, and 30±6% for 100 μg in the warmth and cold immersion test, respectively). In the tail-flick test, the doses of 30, 60 and 100 μg/rat dose-dependently and significantly increased the withdrawal thresholds from 5 to 45 min after the injection, with a maximum effect at 5 min (30±5% for 30 μg; 37±6% for 60 μg; and 45±4% for 100 μg). In the formalin test, 5-HT (10, 25, 50, 75 and 100 μg/rat) produced dose-related antinociception. The nociceptive response (licking of the injected paw) was significantly reduced from 25 μg (−59±11%) in the early phase, whereas the lowest active dose in the late phase was 50 μg (−46±17%). For both phases, a total inhibition was obtained with 100 μg. It is concluded that the effect of 5-HT on pain tests may differ according to the applied stimulus and the parameter assessed; unspecific effects of 5-HT may modify motor reactions to noxious stimuli. Mechanical test (assessment of vocalization) was the most sensitive to 5-HT. These observations are of importance in order to further study the pharmacological mechanisms involved in 5-HT spinally induced antinociception.

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