Padera Robert F, Tse Julie Y, Bellas Evangelia, Kohane Daniel S
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Muscle Nerve. 2006 Dec;34(6):747-53. doi: 10.1002/mus.20618.
Conventional local anesthetics such as bupivacaine cause considerable myotoxicity and neurotoxicity, whereas tetrodotoxin (TTX) does not. Tetrodotoxin combined with bupivacaine or vasoconstrictors produces long-duration nerve blockade. To assess whether these prolonged blocks can be produced without increased myotoxicity, Sprague-Dawley rats were injected with bupivacaine, TTX, and both, or TTX plus epinephrine. Median durations of thermal nociceptive blockade were, respectively, 188, 401, 882, and 972 min. On dissection 4 days later, all tissues appeared macroscopically pristine. Muscle injury was at most mild to moderate in all animals, and the muscle injury scores for the combination formulations were not higher than for bupivacaine alone. Similarly, in differentiated cells from a myoblast cell line (C2C12), TTX caused either no or minimal worsening of cell viability from bupivacaine at 2 or 7 days. Epinephrine did not worsen TTX's relatively minimal cytotoxicity. Tetrodotoxin may thus be useful in producing prolonged nerve block with minimal myotoxicity and perhaps neurotoxicity.
传统的局部麻醉药如布比卡因会引起相当大的肌毒性和神经毒性，而河豚毒素（TTX）则不会。河豚毒素与布比卡因或血管收缩剂联合使用可产生长效神经阻滞。为了评估在不增加肌毒性的情况下是否能产生这些延长的阻滞，给Sprague-Dawley大鼠注射布比卡因、河豚毒素、两者联合，或河豚毒素加肾上腺素。热痛觉阻滞的中位持续时间分别为188、401、882和972分钟。4天后解剖时，所有组织在宏观上看起来都完好无损。所有动物的肌肉损伤至多为轻度至中度，联合制剂的肌肉损伤评分不高于单独使用布比卡因的情况。同样，在成肌细胞系（C2C12）分化的细胞中，在2天或7天时，河豚毒素对布比卡因导致的细胞活力下降没有影响或仅有轻微加重。肾上腺素并未加剧河豚毒素相对较小的细胞毒性。因此，河豚毒素可能有助于在产生长效神经阻滞的同时，使肌毒性和可能的神经毒性降至最低。
