5‐HT2B Receptor Antagonists Reduce Nerve Injury‐Induced Tactile Allodynia and Expression of 5‐HT2B Receptors. Issue 1 (25th January 2015)

• Record Type: Journal Article
• Authors: Pineda‐Farias, Jorge B.; Velázquez‐Lagunas, Isabel; Barragán‐Iglesias, Paulino; Cervantes‐Durán, Claudia; Granados‐Soto, Vinicio
• Is Part Of: Drug development research. Volume 76:Issue 1(2015)
• Page Start: 31
• Page End: 39
• Publication Date: 2015-01-25
• Subjects: Drug development -- Periodicals; Drugs -- Research -- Periodicals; 615.19
• DOI: 10.1002/ddr.21238
• Languages: English
• ISSNs: 0272-4391

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p> <table-wrap position="anchor" orientation="portrait"> <table width="100%" border="1"> <colgroup span="1"> <col span="1" /> </colgroup> <tbody> <tr> <td align="left" rowspan="1" colspan="1">Preclinical Research</td> </tr> </tbody> </table> </table-wrap> </p> <p>This work was performed to assess the effects of intrathecal serotonin 2B (5‐HT<sub>2</sub><sub>B</sub>) receptor antagonists in rats with neuropathic pain. With RS‐127445, its effect was also determined on 5‐HT<sub>2</sub><sub>B</sub> receptor expression. Neuropathic pain was induced by L5/L6 spinal nerve ligation. Western blotting was used to determine 5‐HT<sub>2</sub><sub>B</sub> receptor expression. Dose‐response curves with the 5‐HT<sub>2</sub><sub>B</sub> 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<italic>H</italic>‐pyrido[3, 4‐<italic>b</italic>]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<sub>2</sub><sub>B</sub> receptor antagonists RS‐127445 and LY‐266097 diminished spinal nerve ligation‐induced allodynia. In contrast, intrathecal injection of the 5‐HT<sub>2</sub> 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<sub>2</sub><sub>B</sub> receptors in the ipsilateral, but not contralateral, dorsal root ganglia. Furthermore, nerve injury also enhanced 5‐HT<sub>2</sub><sub>B</sub> 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<sub>2</sub><sub>B</sub> receptors in dorsal root ganglia and spinal cord. Our results imply that spinal 5‐HT<sub>2</sub><sub>B</sub> receptors are present on sites related to nociception and participate in neuropathic pain. © 2014 Wiley Periodicals, Inc Drug Dev Res 76 : 31–39, 2015</p> </abstract>