BJA Advance Access originally published online on May 4, 2006
British Journal of Anaesthesia 2006 96(6):761-768; doi:10.1093/bja/ael096
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Antinociceptive effects of tetrodotoxin (TTX) in rodents
,*
1 Department of Anesthesiology, Faculty of Medicine, Université de Montréal Montréal, Québec, Canada
2 Department of Pharmacology, Faculty of Medicine, Université de Montréal Montréal, Québec, Canada
3 Wex Pharmaceuticals Inc. Vancouver, Canada
4 Beijing Medical University China
*Corresponding author: Department of Anesthesiology, CHUM—Hôtel-Dieu, 3840 rue St-Urbain, Montréal, H2W 1T8, Québec, Canada. E-mail: pierre.beaulieu{at}umontreal.ca
Background. Tetrodotoxin (TTX) is a powerful sodium channel blocker extracted from the puffer fish. The analgesic effects of TTX were investigated in different animal pain models.
Methods. Wistar rats were submitted to the formalin test and to partial ligation of the sciatic nerve (Seltzer's model). Swiss Webster mice were used in the writhing test. Rodents were divided into six groups receiving a s.c. injection of either 0.9% NaCl, TTX 0.3, 1, 3, or 6 µg kg–1, or morphine (5 mg kg–1). Substances were injected 30 min before 2.5% formalin injection into the hind paw, acetic acid administration intraperitoneally or neuropathic pain testing consisting of mechanical allodynia (von Frey filament) and thermal hyperalgesia (Plantar test).
Results. TTX decreased pain behaviour in the formalin test at the highest dose and in the writhing test at 3 and 6 µg kg–1. It also diminished mechanical allodynia and thermal hyperalgesia with an ED50 of 1.08 (0.89) and 0.62 (0.33) µg kg–1, respectively. Observation of the rats after TTX injection did not show any motor deficit, respiratory distress or sedation. Morphine was also effective in relieving pain in all three tests but with signs of considerable sedation.
Conclusion. Systemic injections of TTX diminished pain behaviour in a dose-dependent manner in models of inflammatory, visceral and neuropathic pain without causing adverse events, whereas morphine analgesia was associated with heavy sedation. TTX is a very promising substance for the treatment of various types of pain but needs further evaluation.
These authors contributed equally to this work.
Declaration of Interest. Dr Beaulieu received a subsidy from Wex Pharmaceuticals Inc. for laboratory work using TTX. Dr Ngoc is Chief Scientific Officer of Wex Pharmaceuticals Inc. and Dr Lu is also a scientific officer in the company.
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