Distinct Nav1.7-dependent pain sensations require different sets of sensory and sympathetic neurons.

Published online

Journal Article

Human acute and inflammatory pain requires the expression of voltage-gated sodium channel Nav1.7 but its significance for neuropathic pain is unknown. Here we show that Nav1.7 expression in different sets of mouse sensory and sympathetic neurons underlies distinct types of pain sensation. Ablating Nav1.7 gene (SCN9A) expression in all sensory neurons using Advillin-Cre abolishes mechanical pain, inflammatory pain and reflex withdrawal responses to heat. In contrast, heat-evoked pain is retained when SCN9A is deleted only in Nav1.8-positive nociceptors. Surprisingly, responses to the hotplate test, as well as neuropathic pain, are unaffected when SCN9A is deleted in all sensory neurons. However, deleting SCN9A in both sensory and sympathetic neurons abolishes these pain sensations and recapitulates the pain-free phenotype seen in humans with SCN9A loss-of-function mutations. These observations demonstrate an important role for Nav1.7 in sympathetic neurons in neuropathic pain, and provide possible insights into the mechanisms that underlie gain-of-function Nav1.7-dependent pain conditions.

Full Text

Duke Authors

Cited Authors

  • Minett, MS; Nassar, MA; Clark, AK; Passmore, G; Dickenson, AH; Wang, F; Malcangio, M; Wood, JN

Published Date

  • April 24, 2012

Published In

Volume / Issue

  • 3 /

Start / End Page

  • 791 -

PubMed ID

  • 22531176

Pubmed Central ID

  • 22531176

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/ncomms1795

Language

  • eng

Conference Location

  • England