Spinal 5-HT₄ and 5-HT₆ receptors contribute to the maintenance of neuropathic pain in rats

Background Nerve injury promotes release of 5-HT at the spinal cord. Once released, 5-HT may produce antinociceptive or pronociceptive effects depending of the nature of 5-HT receptors. The purpose of this study was to investigate the participation of spinal 5-HT₄ and 5-HT₆ receptors in the maintenance of neuropathic pain in rats. Methods Tactile allodynia was measured using von Frey hairs in male Wistar rats subjected to L5-L6 spinal nerve injury. Selective 5-HT₄ (GR-113808, 0.01–10 nmol/rat) and 5-HT₆ (SB-258585, 1–1000 nmol/rat) receptor antagonists were administered intrathecally to nerve injured rats. Likewise, the most effective dose of 5-HT₄ (1 nmol/rat) and 5-HT₆ (100 nmol/rat) antagonists were co-administered with their respective agonists (ML-10302, 10–100 nmol/rat and WAY-208466, 100–1000 nmol/rat, respectively). Spinal cord protein expression of both receptors was determined by western blot. Results Intrathecal administration of 5-HT₄ or 5-HT₆ receptor antagonists, but not vehicle, decreased in a dose-dependent manner tactile allodynia in neuropathic rats. Moreover, intrathecal co-administration with the agonists prevented in a dose-dependent manner the antagonists-induced antiallodynic effect. Both 5-HT₄ and 5-HT₆ receptors were expressed in the spinal cord of naïve, sham and neuropathic rats. Nerve injury did not modify expression of any receptor. Conclusions Data suggests that spinal 5-HT₄ and 5-HT₆ receptors are expressed in dorsal spinal cord and they participate in the maintenance of neuropathic pain in rats. In this regard, blockade of these receptors could be a useful strategy to treat neuropathic pain states.