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

Preclinical ResearchThis work was performed to assess the effects of intrathecal serotonin 2B (5‐HT 2 B ) receptor antagonists in rats with neuropathic pain. With RS‐127445, its effect was also determined on 5‐HT 2 B receptor expression. Neuropathic pain was induced by L5/L6 spinal nerve ligation. Western blotting was used to determine 5‐HT 2 B receptor expression. Dose‐response curves with the 5‐HT 2 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‐1 H ‐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‐HT 2 B receptor antagonists RS‐127445 and LY‐266097 diminished spinal nerve ligation‐induced allodynia. In contrast, intrathecal injection of the 5‐HT 2 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‐HT 2 B receptors in the ipsilateral, but not contralateral, dorsal root ganglia. Furthermore, nerve injury also enhanced 5‐HT 2 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‐HT 2 B receptors in dorsal root ganglia and spinal cord. Our results imply that spinal 5‐HT 2 B receptors are present on sites related to nociception and participate in neuropathic pain. © 2014 Wiley Periodicals, Inc Drug Dev Res 76 : 31–39, 2015