5-HT 2B Receptor Antagonists Reduce Nerve Injury-Induced Tactile Allodynia and Expression of 5-HT 2B Receptors

Jorge B Pineda-Farias, Isabel Velázquez-Lagunas, Paulino Barragán-Iglesias, Claudia Cervantes-Durán, Vinicio Granados-Soto
Drug Development Research 2015, 76 (1): 31-39
Preclinical Research This work was performed to assess the effects of intrathecal serotonin 2B (5-HT2 B ) receptor antagonists in rats with neuropathic pain. With RS-127445, its effect was also determined on 5-HT2 B receptor expression. Neuropathic pain was induced by L5/L6 spinal nerve ligation. Western blotting was used to determine 5-HT2 B receptor expression. Dose-response curves with the 5-HT2 B receptor antagonists 2-amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyridine (RS-127445, 1-100 nmol) and 1-[(2-chloro-3,4-dimethoxyphenyl)methyl]-2,3,4,9-tetrahydro-6-methyl-1H-pyrido[3,4-b]indole hydrochloride (LY-266097, 1-100 nmol) were performed in rats. Tactile allodynia of the left hind paw (ipsilateral) was assessed for 8 h after compound administration. Intrathecal injection of the 5-HT2 B receptor antagonists RS-127445 and LY-266097 diminished spinal nerve ligation-induced allodynia. In contrast, intrathecal injection of the 5-HT2 receptor agonist (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI, 10 nmol) did not modify tactile allodynia induced by nerve ligation. L5/L6 nerve ligation increased expression of the 5-HT2 B receptors in the ipsilateral, but not contralateral, dorsal root ganglia. Furthermore, nerve injury also enhanced 5-HT2 B receptor expression in the ipsilateral dorsal part of the spinal cord. Intrathecal treatment with RS-127445 (100 nmol) diminished spinal nerve injury-induced increased expression of 5-HT2 B receptors in dorsal root ganglia and spinal cord. Our results imply that spinal 5-HT2 B receptors are present on sites related to nociception and participate in neuropathic pain. © 2014 Wiley Periodicals, Inc.

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