title: Nav1.7 and other voltage-gated sodium channels as drug targets for pain relief.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Sodium channel subtypes have been linked to human pain syndromes through genetic studies. Gain of function mutations in Nav1.7, 1.8 and 1.9 can cause pain, whilst loss of function Nav1.7 mutations lead to loss of pain in otherwise normal people. Intriguingly, both human and mouse Nav1.7 null mutants have increased opioid drive, because naloxone, an opioid antagonist, can reverse the analgesia associated with the loss of Nav1.7 expression.
  
  
  CONCLUSIONS
  We believe there is a great future for sodium channel antagonists, particularly Nav1.7 antagonists in treating most pain syndromes. This review deals with recent attempts to develop specific sodium channel blockers, the mechanisms that underpin the Nav1.7 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 Nav1.7 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.
authors.affiliation: a Molecular Nociception Group, Department of Medicine , WIBR, University College London , London WC1E 6BT , UK.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Emery
authors.affiliation: a Molecular Nociception Group, Department of Medicine , WIBR, University College London , London WC1E 6BT , UK.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Luiz
authors.affiliation: a Molecular Nociception Group, Department of Medicine , WIBR, University College London , London WC1E 6BT , UK.
authors.forename: John N
authors.initials: JN
authors.lastname: Wood
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D000818:Animals; D059350:Chronic Pain / Q000188:drug therapy* / Q000473:pathology; D015195:Drug Design; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D058990:Molecular Targeted Therapy; D009154:Mutation; D062556:NAV1.7 Voltage-Gated Sodium Channel / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D009270:Naloxone / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D062556:NAV1.7 Voltage-Gated Sodium Channel; C486866:SCN9A protein, human; D026941:Sodium Channel Blockers; D009270:Naloxone
keywords: Nav1.7; SCN9A; opioids; pain; sensory neurons