Sensory neuron voltage-gated sodium channels as analgesic drug targets.
Voltage-gated sodium channels are crucial determinants of neuronal excitability and signalling; some specific channel subtypes have been implicated in a number of chronic pain conditions. Human genetic studies show gain-of-function or loss-of-function mutations in Na(V)1.7 lead to an enhancement or lack of pain, respectively, whilst transgenic mouse and knockdown studies have implicated Na(V)1.3, Na(V)1.8 and Na(V)1.9 in peripheral pain pathways. The development of subtype-specific sodium channel blockers, though clearly desirable, has been technically challenging. Recent advances exploiting both natural products and small molecule selective channel blockers have demonstrated that this approach to pain control is feasible. These observations provide a rationale for the development of new analgesics without the side effect profile of broad spectrum sodium channel blockers.
Momin
Aliakmal
A
Molecular Nociception, Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, United Kingdom. a.momin@ucl.ac.uk
Wood
John N
JN
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D010146:Pain / Q000503:physiopathology / Q000517:prevention & control; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology*
D000700:Analgesics; D026941:Sodium Channel Blockers; D015222:Sodium Channels