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Mar. Drugs 2017, 15(6), 188;

Effects of Tetrodotoxin in Mouse Models of Visceral Pain

Department of Pharmacology, Biomedical Research Centre and Institute of Neuroscience, Faculty of Medicine, University of Granada, 18016 Granada, Spain
Biosanitary Research Institute, University Hospital Complex of Granada, 18012 Granada, Spain
Animal Behavior Research Unit, Scientific Instrumentation Center, University of Granada, Armilla, 18100 Granada, Spain
Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London, London WC1E 6BT, UK
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Received: 5 April 2017 / Revised: 7 June 2017 / Accepted: 16 June 2017 / Published: 21 June 2017
(This article belongs to the Special Issue Tetrodotoxin)
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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. View Full-Text
Keywords: tetrodotoxin; visceral pain; referred mechanical hyperalgesia; TTX-sensitive voltage-gated sodium channels; Nav1.7; capsaicin; mustard oil; cyclophosphamide tetrodotoxin; visceral pain; referred mechanical hyperalgesia; TTX-sensitive voltage-gated sodium channels; Nav1.7; capsaicin; mustard oil; cyclophosphamide

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González-Cano, R.; Tejada, M.Á.; Artacho-Cordón, A.; Nieto, F.R.; Entrena, J.M.; Wood, J.N.; Cendán, C.M. Effects of Tetrodotoxin in Mouse Models of Visceral Pain. Mar. Drugs 2017, 15, 188.

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