Serotonin receptor subtypes involved in the spinal antinociceptive effect of 5-HT in rats

The present study was designed to investigate which subtypes of spinal 5-HT receptors are involved in 5-MT-induced antinociception using the mechanica l pain test. Serotonin and various selective antagonists or agonists for 5- HT receptor subtypes (5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C, 5-HT3 and 5-HT4) were administered intrathecally (i.t.) in rats. The i.t. injection of 5-HT (1 m u g) produced significant antinociceptive effects using the paw pressure te st. Pretreatment with the 5-HT2C receptor antagonist mesulergine (1 and 10 mu g) and the 5-HT3 receptor antagonist tropisetron (1 and 10 mu g) reverse d totally the antinociception induced by 5-HT. Furthermore, at a dose of 10 mu g, both the 5-HT2A receptor antagonist ketanserin and the 5-HT1B recept or antagonist penbutolol, but neither the 5-HT1A receptor antagonist WAY 10 0635 nor the 5-HT4 receptor antagonist GR113808, attenuated the antinocicep tive effect induced by 5-HT. In addition, an i.t. injection of the 5-HT3 ag onist mCPBG induced significant antinociceptive effects whereas the 5-HT2 a gonist DOI did not produce analgesia. These results suggest that although t he precise degree of the involvement of spinal serotonergic 5-HT3 receptors remains to be elucidated due to some differences in the effect of agonists or antagonists, these receptors seem to play a role in the antinociceptive effect of 5-HT against a mechanical acute noxious stimulus. The involvemen t of 5-HT2C is more questionable due to the observed discrepancies between the effects of the used agonist and antagonist. 5-HT1A and 5-HT4 receptors do not seem to be involved. In addition, a possible functional interaction between spinal serotonergic receptors may exist. (C) 2000 International Ass ociation for the Study of Pain. Published by Elsevier Science B.V. All righ ts reserved.