Effects of Tetrodotoxin in Mouse Models of Visceral Pain
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AuthorGonzález-Cano, Rafael; Tejada, Miguel Ángel; Artacho-Cordón, Antonia; Nieto López, Francisco Rafael; Entrena Fernández, José Manuel; Wood, John N.; Cendán Martínez, Cruz Miguel
TetrodotoxinVisceral painReferred mechanical hyperalgesiaTTX-sensitive voltage-gated sodium channelsNav1.7CapsaicinMustard oilCyclophosphamide
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]
SponsorshipR. González-Cano was supported by a postdoctoral grant from the Contratos-Puente Research Program of the University of Granada. M.A. Tejada was supported by a predoctoral grant from the University of Granada. F. R. Nieto was supported by a postdoctoral Juan de la Cierva grant (Spanish Goverment). This study was partially supported by grant GREIB (CEB-005) from the University of Granada and grant CTS 109 from the Junta de Andalucía.
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.