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Na(v)1.7 and other voltage-gated sodium channels as drug targets for pain relief
Introduction: Chronic pain is a massive clinical problem. We discuss the potential of subtype selective sodium channel blockers that may provide analgesia with limited side effects. Areas covered: Sodium channel subtypes have been linked to human pain syndromes through genetic studies. Gain of funct...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4950419/ https://www.ncbi.nlm.nih.gov/pubmed/26941184 http://dx.doi.org/10.1517/14728222.2016.1162295 |
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author | Emery, Edward C Luiz, Ana Paula Wood, John N |
author_facet | Emery, Edward C Luiz, Ana Paula Wood, John N |
author_sort | Emery, Edward C |
collection | PubMed |
description | Introduction: Chronic pain is a massive clinical problem. We discuss the potential of subtype selective sodium channel blockers that may provide analgesia with limited side effects. Areas covered: Sodium channel subtypes have been linked to human pain syndromes through genetic studies. Gain of function mutations in Na(v)1.7, 1.8 and 1.9 can cause pain, whilst loss of function Na(v)1.7 mutations lead to loss of pain in otherwise normal people. Intriguingly, both human and mouse Na(v)1.7 null mutants have increased opioid drive, because naloxone, an opioid antagonist, can reverse the analgesia associated with the loss of Na(v)1.7 expression. Expert Opinion: We believe there is a great future for sodium channel antagonists, particularly Na(v)1.7 antagonists in treating most pain syndromes. This review deals with recent attempts to develop specific sodium channel blockers, the mechanisms that underpin the Na(v)1.7 null pain-free phenotype and new routes to analgesia using, for example, gene therapy or combination therapy with subtype specific sodium channel blockers and opioids. The use of selective Na(v)1.7 antagonists together with either enkephalinase inhibitors or low dose opioids has the potential for side effect-free analgesia, as well as an important opioid sparing function that may be clinically very significant. |
format | Online Article Text |
id | pubmed-4950419 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-49504192016-08-05 Na(v)1.7 and other voltage-gated sodium channels as drug targets for pain relief Emery, Edward C Luiz, Ana Paula Wood, John N Expert Opin Ther Targets Review Introduction: Chronic pain is a massive clinical problem. We discuss the potential of subtype selective sodium channel blockers that may provide analgesia with limited side effects. Areas covered: Sodium channel subtypes have been linked to human pain syndromes through genetic studies. Gain of function mutations in Na(v)1.7, 1.8 and 1.9 can cause pain, whilst loss of function Na(v)1.7 mutations lead to loss of pain in otherwise normal people. Intriguingly, both human and mouse Na(v)1.7 null mutants have increased opioid drive, because naloxone, an opioid antagonist, can reverse the analgesia associated with the loss of Na(v)1.7 expression. Expert Opinion: We believe there is a great future for sodium channel antagonists, particularly Na(v)1.7 antagonists in treating most pain syndromes. This review deals with recent attempts to develop specific sodium channel blockers, the mechanisms that underpin the Na(v)1.7 null pain-free phenotype and new routes to analgesia using, for example, gene therapy or combination therapy with subtype specific sodium channel blockers and opioids. The use of selective Na(v)1.7 antagonists together with either enkephalinase inhibitors or low dose opioids has the potential for side effect-free analgesia, as well as an important opioid sparing function that may be clinically very significant. Taylor & Francis 2016-08-02 2016-04-12 /pmc/articles/PMC4950419/ /pubmed/26941184 http://dx.doi.org/10.1517/14728222.2016.1162295 Text en © 2016 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group http://creativecommons.org/licenses/by/4.0/ 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 cited. |
spellingShingle | Review Emery, Edward C Luiz, Ana Paula Wood, John N Na(v)1.7 and other voltage-gated sodium channels as drug targets for pain relief |
title | Na(v)1.7 and other voltage-gated sodium channels as drug targets for pain relief |
title_full | Na(v)1.7 and other voltage-gated sodium channels as drug targets for pain relief |
title_fullStr | Na(v)1.7 and other voltage-gated sodium channels as drug targets for pain relief |
title_full_unstemmed | Na(v)1.7 and other voltage-gated sodium channels as drug targets for pain relief |
title_short | Na(v)1.7 and other voltage-gated sodium channels as drug targets for pain relief |
title_sort | na(v)1.7 and other voltage-gated sodium channels as drug targets for pain relief |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4950419/ https://www.ncbi.nlm.nih.gov/pubmed/26941184 http://dx.doi.org/10.1517/14728222.2016.1162295 |
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