Evaluation of the Role of 5-Hydroxytryptamine Receptor Subtypes in the Regulation of Nociceptive Transmission in the Rat Spinal Cord

Background: Spinal 5-hydroxytryptamine (5-HT) has been shown to display an antinociceptive effect, which is mediated by 5-HT receptors. Previous studies have revealed the presence of at least four types of 5-HT receptors in the spinal cord. The aim of this study was to assess the role of each spinal 5-HT receptor in the antinociception of intrathecal 5-HT using the formalin test. Methods: Rats were implanted with lumbar intrathecal catheters. After the administration of 5-HT, formalin-induced nociceptive behavior (flinching response) was observed for 60 min. To further clarify the role of the 5-HT receptors in the antinociception of 5-HT, several antagonists of 5-HT receptors were administered intrathecally 10 min before 5-HT delivery, and formalin was injected 10 min later. Results: Intrathecal 5-HT dose-dependently suppressed flinching during phase 1 and 2 in the formalin test. (GR 55562), (N-desmethylclozapine), (LY-278,584) and (SDZ-205,557) receptors antagonists reversed this antinociception by 5-HT during both phases in the formalin test. receptor antagonist (WAY-100635) decreased antinociception by 5-HT in phase 2, but not in phase 1. A $5-HT_{1D}$ receptor antagonist (BRL 15572) did not antagonize the antinociception of 5-HT in either phases. Conclusions: Spinal 5- receptors, but not the 5- receptor, are involved in the antinociception of serotonin in the facilitated state and in the acute pain evoked by a formalin stimulus. The 5- receptor seems to play a role in 5-HT-induced antinociception in the facilitated state.