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

AbstractWhile 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 40μg) 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 5μg), mianserin (5-HT2 and 5-HT6 antagonist; 0.1μg), isamoltane (5-HT1B antagonist; 0.5 or 5μg) and ketanserin (5-HT2A antagonist; 0.1 or 1μg), but not by BRL 15572 (5-HT1D antagonist; 1 or 10μg), ondansetron (5-HT3 antagonist; 1, 5, 10 or 20μg) and SB 269970 (5-HT7 antagonist; 2.5 and 25μg). 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