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. © 2017 institute of pharmacology,polish academy of sciences