Minett, M.S., Nassar, M.A., Clark, A.K. et al. (5 more authors) (2012) Distinct Nav1.7-dependent pain sensations require different sets of sensory and sympathetic neurons. NATURE COMMUNICATIONS, 3. 791.
Abstract
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.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2012 Macmillan Publishers Limited. This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/). |
Keywords: | Nervous system; Neuropathic pain; Sodium channels; Target identification |
Dates: |
|
Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 22 Mar 2017 14:30 |
Last Modified: | 22 Mar 2017 14:30 |
Published Version: | https://doi.org/10.1038/ncomms1795 |
Status: | Published |
Publisher: | Nature Publishing Group |
Refereed: | Yes |
Identification Number: | 10.1038/ncomms1795 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:113811 |
Download
Licence: CC-BY-NC-ND 3.0