The analgesic agent tapentadol inhibits calcitonin gene-related peptide release from isolated rat brainstem via a serotonergic mechanism

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5 Citazioni (Scopus)

Abstract

Aims: In this study we tested the hypothesis that tapentadol inhibits GGRP release from the rat brainstem through a mechanism mediated by the inhibition of NA reuptake; as a second alternative hypothesis, we investigated whether tapentadol inhibits GGRP release via the inhibition of 5-HT reuptake. Methods: Rat brainstems were explanted and incubated in short-term experiments. CGRP released in the incubation medium was taken as a marker of CGRP release from the central terminals of trigeminal neurons within the brainstem. CGRP levels were measured by radioimmunoassay under basal conditions or in the presence of tapentadol; NA, 5-HT, clonidine, yohimbine and ondansetron were used as pharmacological tools to investigate the action mechanism of tapentadol. Results: The α2-antagonist yohimbine failed to counteract the effects of tapentadol. Moreover, neither NA nor the α2-agonist clonidine per se inhibited K(+)-stimulated CGRP release, thereby indicating that the effects of tapentadol are nor mediated through the block of NA reuptake. Further experiments showed that 5-HT and tramadol, which inhibits both NA and 5-HT reuptake, significantly reduced K(+)-stimulated CGRP release. Moreover, the 5-HT3 antagonist ondansetron was able to counteract the effects of tapentadol in this system. Significance: This study provided pharmacological evidence that tapentadol inhibits stimulated CGRP release from the rat brainstem in vitro through a mechanism involving an increase in 5-HT levels in the system and the subsequent activation of 5-HT3 receptors.
Lingua originaleEnglish
pagine (da-a)161-165
Numero di pagine5
RivistaLife Sciences
Volume2016
DOI
Stato di pubblicazionePubblicato - 2016

Keywords

  • 5-hydroxytryptamine
  • Analgesics
  • Animals
  • Brain Stem
  • Brainstem
  • Calcitonin Gene-Related Peptide
  • Calcitonin gene-related peptide
  • Male
  • Norepinephrine
  • Ondansetron
  • Phenols
  • Potassium
  • Rat
  • Rats
  • Rats, Wistar
  • Serotonin
  • Tapentadol

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