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Papers of the Week


Papers: 28 Sep 2019 - 4 Oct 2019


Pharmacology/Drug Development


2019


J Pain Res


12

Voltage gated sodium channels as therapeutic targets for chronic pain.

Authors

Ma R S Y, Kayani K, Whyte-Oshodi D, Whyte-Oshodi A, Nachiappan N, Gnanarajah S, Mohammed R
J Pain Res. 2019; 12:2709-2722.
PMID: 31564962.

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.