Antinociceptive effect of (-)-epicatechin in inflammatory and neuropathic pain in rats

Geovanna N. Quinõnez-Bastidas, Jorge B. Pineda-Farias, Francisco J. Flores-Murrieta, Juan Rodriguez-Silverio, Juan G. Reyes-Garcia, Beatriz Godínez-Chaparro, Vinicio Granados-Soto, Héctor I. Rocha-Gonzalez

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15 Scopus citations

Abstract

The aim of this study was to investigate the antinociceptive potential of (.)-epicatechin and the possible mechanisms of action involved in its antinociceptive effect. The carrageenan and formalin tests were used as inflammatory pain models. A plethysmometer was used to measure inflammation and L5/L6 spinal nerve ligation as a neuropathic pain model. Oral (-)-epicatechin reduced carrageenan-induced inflammation and nociception by about 59 and 73%, respectively, and reduced formalininduced and nerve injury-induced nociception by about 86 and 43%, respectively. (-)-Epicatechin-induced antinociception in the formalin test was prevented by the intraperitoneal administration of antagonists: Methiothepin (5-HT 1/5 receptor), WAY-100635 (5-HT 1A receptor), SB-224289 (5-HT 1B receptor), BRL-15572 (5-HT 1D receptor), SB-699551 (5-HT 5A receptor), naloxone (opioid receptor), CTAP (κopioid receptor), nor-binaltorphimine (δ 1 opioid receptor), and 7-benzylidenenaltrexone (δ 1 opioid receptor). The effect of (-)-epicatechin was also prevented by the intraperitoneal administration of L-NAME [nitric oxide (NO) synthase inhibitor], 7-nitroindazole (neuronal NO synthase inhibitor), ODQ (guanylyl cyclase inhibitor), glibenclamide (ATP-sensitive K + channel blocker), 4-aminopyridine (voltage-dependent K + channel blocker), and iberiotoxin (large-conductance Ca 2+ -activated K+ channel blocker), but not by amiloride (acid sensing ion channel blocker). The data suggest that (-)-epicatechin exerts its antinociceptive effects by activation of the NO-cyclic GMP-K+ channels pathway, 5-HT 1A/1B/1D/5A serotonergic receptors, and μ/κ/δ opioid receptors.

Original languageEnglish
Pages (from-to)270-279
Number of pages10
JournalBehavioural Pharmacology
Volume29
DOIs
StatePublished - 5 Jun 2018

Keywords

  • (-)-epicatechin
  • ASICs
  • inflammation
  • nitric oxide
  • nociception
  • opioids
  • pain
  • serotonin

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