Peripheral 5-HT1B and 5-HT2A receptors mediate the nociceptive response induced by 5-hydroxytryptamine in mice

While the role of 5-hydroxytryptamine (5-HT, serotonin) in the nociceptive processing has been widely investigated in the central nervous system, information regarding its role in peripheral tissues is still lacking. Noteworthy, 5-HT induces phenotypic changes of nociceptors and peripheral injection induces pain in humans and nociceptive response in rodents. However, local receptors involved in 5-HT effects are not well characterized. Thus, we aimed to investigate the role of 5-HT and some of its receptors in the peripheral nociceptive processing in mice. Intraplantar injection of 5-HT (10, 20 or 40 mu g) into the hind-paw of mice induced paw licking behavior, which was inhibited by previous intraplantar treatment with cyproheptadine (5-HT1 and 5-HT2 antagonist; 0.5 or 5 mu g), mianserin (5-HT2 and 5-HT6 antagonist; 0.1 mu g), isamoltane (5-HT1B antagonist; 0.5 or 5 mu g) and ketanserin (5-HT2A antagonist; 0.1 or 1 mu g), but not by BRL 15572 (5-HT1D antagonist; 1 or 10 mu g), ondansetron (5-HT3 antagonist; 1, 5, 10 or 20 mu g) and SB 269970 (5-HT7 antagonist; 2.5 and 25 mu g). Altogether, these results indicate the local involvement of 5-HT1, 5-HT2 and 5-HT6, especially 5-HT1B and 5-HT2A, in the nociceptive response induced by 5-HT in mice, thus contributing to a better understanding of 5-HT role in the peripheral nociceptive processing. In addition, they also point to important species differences and the need of a wide evaluation of the peripheral nociceptive processing in mice as these animals have been increasingly used in studies investigating the cellular and molecular mechanisms mediating the nociceptive response. (C) 2011 Elsevier Inc. All rights reserved.