Marcil J, Walczak J-S, Guindon J, Ngoc A H, Lu S, Beaulieu P
Department of Anesthesiology, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.
Br J Anaesth. 2006 Jun;96(6):761-8. doi: 10.1093/bja/ael096. Epub 2006 May 4.
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.
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 microg 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).
TTX decreased pain behaviour in the formalin test at the highest dose and in the writhing test at 3 and 6 microg kg(-1). It also diminished mechanical allodynia and thermal hyperalgesia with an ED(50) of 1.08 (0.89) and 0.62 (0.33) microg 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.
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.
河豚毒素（TTX）是一种从河豚中提取的强效钠通道阻滞剂。在不同的动物疼痛模型中研究了TTX的镇痛作用。
将Wistar大鼠用于福尔马林试验和坐骨神经部分结扎（塞尔策模型）。瑞士韦伯斯特小鼠用于扭体试验。将啮齿动物分为六组，分别皮下注射0.9%氯化钠、0.3、1、3或6微克/千克的TTX，或吗啡（5毫克/千克）。在向大鼠后爪注射2.5%福尔马林、腹腔注射醋酸或进行由机械性异常性疼痛（von Frey细丝）和热痛觉过敏（足底试验）组成的神经性疼痛测试前30分钟注射这些物质。
TTX在最高剂量时可减轻福尔马林试验中的疼痛行为，在3和6微克/千克时可减轻扭体试验中的疼痛行为。它还能减轻机械性异常性疼痛和热痛觉过敏，其半数有效剂量（ED50）分别为1.08（0.89）和0.62（0.33）微克/千克。注射TTX后观察大鼠未发现任何运动缺陷、呼吸窘迫或镇静迹象。吗啡在所有三项试验中也能有效缓解疼痛，但有明显的镇静迹象。
全身注射TTX在炎症性、内脏性和神经性疼痛模型中以剂量依赖性方式减轻疼痛行为，且不引起不良事件，而吗啡镇痛则伴有严重镇静。TTX是一种治疗各种类型疼痛的非常有前景的物质，但需要进一步评估。
