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Voltage gated sodium channels as therapeutic targets for chronic pain

Authors Ma RSY, Kayani K, Whyte-Oshodi D, Whyte-Oshodi A, Nachiappan N, Gnanarajah S, Mohammed R

Received 5 March 2019

Accepted for publication 2 August 2019

Published 9 September 2019 Volume 2019:12 Pages 2709—2722

DOI https://doi.org/10.2147/JPR.S207610

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr Michael Ueberall


Renee Siu Yu Ma,1 Kayani Kayani,1 Danniella Whyte-Oshodi,1 Aiyesha Whyte-Oshodi,2 Nitish Nachiappan,3 Shaene Gnanarajah,1 Raihan Mohammed1

1Department of Medicine, University of Cambridge, Cambridge, UK; 2Faculty of Medicine, University College London, London, UK; 3Faculty of Medicine, Imperial College London, London, UK

Correspondence: Raihan Mohammed
School of Clinical Medicine, University of Cambridge, Hills Road, Cambridge CB2 0SP, UK
Tel +44 787 173 6004
Email rm758@cam.ac.uk

Abstract: Being maladaptive and frequently unresponsive to pharmacotherapy, chronic pain presents a major unmet clinical need. While an intact central nervous system is required for conscious pain perception, nociceptor hyperexcitability induced by nerve injury in the peripheral nervous system (PNS) is sufficient and necessary to initiate and maintain neuropathic pain. The genesis and propagation of action potentials is dependent on voltage-gated sodium channels, in particular, Nav1.7, Nav1.8 and Nav1.9. However, nerve injury triggers changes in their distribution, expression and/or biophysical properties, leading to aberrant excitability. Most existing treatment for pain relief acts through non-selective, state-dependent sodium channel blockage and have narrow therapeutic windows. Natural toxins and developing subtype-specific and molecular-specific sodium channel blockers show promise for treatment of neuropathic pain with minimal side effects. New approaches to analgesia include combination therapy and gene therapy. Here, we review how individual sodium channel subtypes contribute to pain, and the attempts made to develop more effective analgesics for the treatment of chronic pain.

Keywords: nociceptors, TTX, neuropathic, electrogenesis, CNS, PNS
 

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