Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/130018
Citations
Scopus Web of Science® Altmetric
?
?
Type: Journal article
Title: Pharmacological modulation of voltage-gated sodium (Na(V)) channels alters nociception arising from the female reproductive tract
Author: Castro, J.
Maddern, J.
Erickson, A.
Caldwell, A.
Grundy, L.
Harrington, A.M.
Brierley, S.M.
Citation: Pain, 2021; 162(1):227-242
Publisher: Wolters Kluwer; International Association for the Study of Pain
Issue Date: 2021
ISSN: 0304-3959
1872-6623
Statement of
Responsibility: 
Joel Castro, Jessica Maddern, Andelain Erickson, Ashlee Caldwell, Luke Grundy, Andrea M. Harrington, Stuart M. Brierley
Abstract: Dyspareunia, also known as vaginal hyperalgesia, is a prevalent and debilitating symptom of gynaecological disorders such as endometriosis and vulvodynia. Despite this, the sensory pathways transmitting nociceptive information from female reproductive organs remain poorly characterised. As such, the development of specific treatments for pain associated with dyspareunia is currently lacking. Here, we examined, for the first time, (1) the mechanosensory properties of pelvic afferent nerves innervating the mouse vagina; (2) the expression profile of voltage-gated sodium (NaV) channels within these afferents; and (3) how pharmacological modulation of these channels alters vaginal nociceptive signalling ex vivo, in vitro, and in vivo. We developed a novel afferent recording preparation and characterised responses of pelvic afferents innervating the mouse vagina to different mechanical stimuli. Single-cell reverse transcription-polymerase chain reaction determined mRNA expression of NaV channels within vagina-innervating dorsal root ganglia neurons. Vagina-innervating dorsal root ganglia neuroexcitability was measured using whole-cell patch-clamp electrophysiology. Nociception evoked by vaginal distension was assessed by dorsal horn neuron activation within the spinal cord and quantification of visceromotor responses. We found that pelvic afferents innervating the vagina are tuned to detect various mechanical stimuli, with NaV channels abundantly expressed within these neurons. Pharmacological modulation of NaV channels (with veratridine or tetrodotoxin) correspondingly alters the excitability and mechanosensitivity of vagina-innervating afferents, as well as dorsal horn neuron activation and visceromotor responses evoked by vaginal distension. This study identifies potential molecular targets that can be used to modulate vaginal nociceptive signalling and aid in the development of approaches to manage endometriosis and vulvodynia-related dyspareunia.
Keywords: Dyspareunia; endometriosis; vulvodynia; vagina-innervating sensory neurons; vaginal afferents; visceromotor response; vaginal distension; mechanosensitivity
Rights: © 2020 by the International Association for the Study of Pain.
DOI: 10.1097/j.pain.0000000000002036
Grant ID: http://purl.org/au-research/grants/nhmrc/1181448
http://purl.org/au-research/grants/nhmrc/1126378
http://purl.org/au-research/grants/nhmrc/1083480
http://purl.org/au-research/grants/nhmrc/1139366
http://purl.org/au-research/grants/nhmrc/1140297
http://purl.org/au-research/grants/arc/DE130100223
http://purl.org/au-research/grants/arc/DP180101395
Published version: http://dx.doi.org/10.1097/j.pain.0000000000002036
Appears in Collections:Aurora harvest 4
Medicine publications

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.