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N-acetyl-cysteine, a drug that enhances the endogenous activation of group-II metabotropic glutamate receptors, inhibits nociceptive transmission in humans
BACKGROUND: Emerging research seeking novel analgesic drugs focuses on agents targeting group-II metabotropic glutamate receptors (mGlu2 and mGlu3 receptors). N-Acetylcysteine (NAC) enhances the endogenous activation of mGlu2/3 receptors by activating the glial glutamate:cystine membrane exchanger....
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4379592/ https://www.ncbi.nlm.nih.gov/pubmed/25889381 http://dx.doi.org/10.1186/s12990-015-0009-2 |
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author | Truini, Andrea Piroso, Serena Pasquale, Erica Notartomaso, Serena Di Stefano, Giulia Lattanzi, Roberta Battaglia, Giuseppe Nicoletti, Ferdinando Cruccu, Giorgio |
author_facet | Truini, Andrea Piroso, Serena Pasquale, Erica Notartomaso, Serena Di Stefano, Giulia Lattanzi, Roberta Battaglia, Giuseppe Nicoletti, Ferdinando Cruccu, Giorgio |
author_sort | Truini, Andrea |
collection | PubMed |
description | BACKGROUND: Emerging research seeking novel analgesic drugs focuses on agents targeting group-II metabotropic glutamate receptors (mGlu2 and mGlu3 receptors). N-Acetylcysteine (NAC) enhances the endogenous activation of mGlu2/3 receptors by activating the glial glutamate:cystine membrane exchanger. Here, we examined whether NAC inhibits nociceptive responses in humans and animals. We tested the effect of oral NAC (1.2 g) on thermal-pain thresholds and laser-evoked potentials in 10 healthy volunteers, according to a crossover, double-blind, placebo-controlled design, and the effect of NAC (100 mg/kg, i.p.) on the tail-flick response evoked by radiant heat stimulation in mice. RESULTS: In healthy subjects, NAC treatment left thermal-pain thresholds unchanged, but significantly reduced pain ratings to laser stimuli and amplitudes of laser-evoked potentials. NAC induced significantly greater changes in these measures than placebo. In the tail-flick test, NAC strongly reduced the nocifensive reflex response to radiant heat. The action of NAC was abolished by the preferential mGlu2/3 receptor antagonist, LY341495 (1 mg/kg, i.p.). CONCLUSIONS: Our findings show for the first time that NAC inhibits nociceptive transmission in humans, and does the same in mice by activating mGlu2/3 receptors. These data lay the groundwork for investigating the therapeutic potential of NAC in patients with chronic pain. |
format | Online Article Text |
id | pubmed-4379592 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-43795922015-04-01 N-acetyl-cysteine, a drug that enhances the endogenous activation of group-II metabotropic glutamate receptors, inhibits nociceptive transmission in humans Truini, Andrea Piroso, Serena Pasquale, Erica Notartomaso, Serena Di Stefano, Giulia Lattanzi, Roberta Battaglia, Giuseppe Nicoletti, Ferdinando Cruccu, Giorgio Mol Pain Research BACKGROUND: Emerging research seeking novel analgesic drugs focuses on agents targeting group-II metabotropic glutamate receptors (mGlu2 and mGlu3 receptors). N-Acetylcysteine (NAC) enhances the endogenous activation of mGlu2/3 receptors by activating the glial glutamate:cystine membrane exchanger. Here, we examined whether NAC inhibits nociceptive responses in humans and animals. We tested the effect of oral NAC (1.2 g) on thermal-pain thresholds and laser-evoked potentials in 10 healthy volunteers, according to a crossover, double-blind, placebo-controlled design, and the effect of NAC (100 mg/kg, i.p.) on the tail-flick response evoked by radiant heat stimulation in mice. RESULTS: In healthy subjects, NAC treatment left thermal-pain thresholds unchanged, but significantly reduced pain ratings to laser stimuli and amplitudes of laser-evoked potentials. NAC induced significantly greater changes in these measures than placebo. In the tail-flick test, NAC strongly reduced the nocifensive reflex response to radiant heat. The action of NAC was abolished by the preferential mGlu2/3 receptor antagonist, LY341495 (1 mg/kg, i.p.). CONCLUSIONS: Our findings show for the first time that NAC inhibits nociceptive transmission in humans, and does the same in mice by activating mGlu2/3 receptors. These data lay the groundwork for investigating the therapeutic potential of NAC in patients with chronic pain. BioMed Central 2015-03-20 /pmc/articles/PMC4379592/ /pubmed/25889381 http://dx.doi.org/10.1186/s12990-015-0009-2 Text en © Truini et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Truini, Andrea Piroso, Serena Pasquale, Erica Notartomaso, Serena Di Stefano, Giulia Lattanzi, Roberta Battaglia, Giuseppe Nicoletti, Ferdinando Cruccu, Giorgio N-acetyl-cysteine, a drug that enhances the endogenous activation of group-II metabotropic glutamate receptors, inhibits nociceptive transmission in humans |
title | N-acetyl-cysteine, a drug that enhances the endogenous activation of group-II metabotropic glutamate receptors, inhibits nociceptive transmission in humans |
title_full | N-acetyl-cysteine, a drug that enhances the endogenous activation of group-II metabotropic glutamate receptors, inhibits nociceptive transmission in humans |
title_fullStr | N-acetyl-cysteine, a drug that enhances the endogenous activation of group-II metabotropic glutamate receptors, inhibits nociceptive transmission in humans |
title_full_unstemmed | N-acetyl-cysteine, a drug that enhances the endogenous activation of group-II metabotropic glutamate receptors, inhibits nociceptive transmission in humans |
title_short | N-acetyl-cysteine, a drug that enhances the endogenous activation of group-II metabotropic glutamate receptors, inhibits nociceptive transmission in humans |
title_sort | n-acetyl-cysteine, a drug that enhances the endogenous activation of group-ii metabotropic glutamate receptors, inhibits nociceptive transmission in humans |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4379592/ https://www.ncbi.nlm.nih.gov/pubmed/25889381 http://dx.doi.org/10.1186/s12990-015-0009-2 |
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