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Papers of the Week


Papers: 27 Mar 2021 - 2 Apr 2021


2021 Mar 29


Nat Rev Neurosci

Editor's Pick

The physiological function of different voltage-gated sodium channels in pain.

Authors

Goodwin G, McMahon SB
Nat Rev Neurosci. 2021 Mar 29.
PMID: 33782571.

Abstract

Evidence from human genetic pain disorders shows that voltage-gated sodium channel α-subtypes Nav1.7, Nav1.8 and Nav1.9 are important in the peripheral signalling of pain. Nav1.7 is of particular interest because individuals with Nav1.7 loss-of-function mutations are congenitally insensitive to acute and chronic pain, and there is considerable hope that phenocopying these effects with a pharmacological antagonist will produce a new class of analgesic drug. However, studies in these rare individuals do not reveal how and where voltage-gated sodium channels contribute to pain signalling, which is of critical importance for drug development. More than a decade of research utilizing rodent genetic models and pharmacological tools to study voltage-gated sodium channels in pain has begun to unravel the role of different subtypes. Here, we review the contribution of individual channel subtypes in three key physiological processes necessary for transmission of sensory information to the CNS: transduction of stimuli at peripheral nerve terminals, axonal transmission of action potentials and neurotransmitter release from central terminals. These data suggest that drugs seeking to recapitulate the analgesic effects of loss of function of Nav1.7 will need to be brain-penetrant – which most of those developed to date are not.