Effects of Tetrodotoxin in Mouse Models of Visceral Pain González-Cano, Rafael Tejada, Miguel Ángel Artacho Cordón, Antonia Nieto López, Francisco Rafael Entrena Fernández, José Manuel Wood, John N. Cendán Martínez, Cruz Miguel Tetrodotoxin Visceral pain Referred mechanical hyperalgesia TTX-sensitive voltage-gated sodium channels Nav1.7 Capsaicin Mustard oil Cyclophosphamide 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. 2017-07-27T10:54:43Z 2017-07-27T10:54:43Z 2017-06-21 info:eu-repo/semantics/article González-Cano, R.; et al. Effects of Tetrodotoxin in Mouse Models of Visceral Pain. Marine Drugs, 15(6): 188 (2017). [http://hdl.handle.net/10481/47288] 1660-3397 http://hdl.handle.net/10481/47288 10.3390/md15060188 eng http://creativecommons.org/licenses/by-nc-nd/3.0/ info:eu-repo/semantics/openAccess Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License MDPI