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Effects of Tetrodotoxin in Mouse Models of Visceral Pain

González-Cano, R; Tejada, MÁ; Artacho-Cordón, A; Nieto, FR; Entrena, JM; Wood, JN; Cendán, CM; (2017) Effects of Tetrodotoxin in Mouse Models of Visceral Pain. Marine Drugs , 15 (6) , Article 188. 10.3390/md15060188. Green open access

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Abstract

Visceral pain is very common and represents a major unmet clinical need for which current pharmacological treatments are often insufficient. Tetrodotoxin (TTX) is a potent neurotoxin that exerts analgesic actions in both humans and rodents under different somatic pain conditions, but its effect has been unexplored in visceral pain. Therefore, we tested the effects of systemic TTX in viscero-specific mouse models of chemical stimulation of the colon (intracolonic instillation of capsaicin and mustard oil) and intraperitoneal cyclophosphamide-induced cystitis. The subcutaneous administration of TTX dose-dependently inhibited the number of pain-related behaviors in all evaluated pain models and reversed the referred mechanical hyperalgesia (examined by stimulation of the abdomen with von Frey filaments) induced by capsaicin and cyclophosphamide, but not that induced by mustard oil. Morphine inhibited both pain responses and the referred mechanical hyperalgesia in all tests. Conditional nociceptor‑specific Nav1.7 knockout mice treated with TTX showed the same responses as littermate controls after the administration of the algogens. No motor incoordination after the administration of TTX was observed. These results suggest that blockade of TTX-sensitive sodium channels, but not Nav1.7 subtype alone, by systemic administration of TTX might be a potential therapeutic strategy for the treatment of visceral pain.

Type: Article
Title: Effects of Tetrodotoxin in Mouse Models of Visceral Pain
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/md15060188
Publisher version: http://doi.org/10.3390/md15060188
Language: English
Additional information: Copyright © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Keywords: tetrodotoxin; visceral pain; referred mechanical hyperalgesia; TTX-sensitive voltage-gated sodium channels; Nav1.7; capsaicin; mustard oil; cyclophosphamide
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research
URI: https://discovery.ucl.ac.uk/id/eprint/1561077
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