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Spinal 5-HT 4 and 5-HT 6 receptors contribute to the maintenance of neuropathic pain in rats

Spinal 5-HT 4 and 5-HT 6 receptors contribute to the maintenance of neuropathic pain in rats

Jorge Baruch Pineda-Farias, Paulino Barragán-Iglesias, Alann Valdivieso-Sánchez, Juan Rodríguez-Silverio, Francisco Javier Flores-Murrieta, Vinicio Granados-Soto, Héctor Isaac Rocha-González

Pharmacol Rep. 2017 Oct;69(5):916-923.

PMID: 28628851

Abstract:

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, 0.01-10nmol/rat) and 5-HT6 (SB-258585, 1-1000nmol/rat) receptor antagonists were administered intrathecally to nerve injured rats. Likewise, the most effective dose of 5-HT4 (1nmol/rat) and 5-HT6 (100 nmol/rat) antagonists were co-administered with their respective agonists (ML-10302, 10-100nmol/rat and WAY-208466, 100-1000nmol/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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP148868557	ML 10302		148868-55-7	Price

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