Schwartz D M, Duncan K G, Fields H L, Jones M R
UCSF, Department of Ophthalmology 94143, USA.
Graefes Arch Clin Exp Ophthalmol. 1998 Oct;236(10):790-4. doi: 10.1007/s004170050160.
Tetrodotoxin (TTX) binds with high affinity to sodium channels and produces local anesthesia. We investigated whether TTX is an effective, long-acting corneal anesthetic in rabbits.
After mechanical debridement of the central corneal epithelium, topical TTX (1 mM, 0.1 mM, or 0.01 mM) was applied to one eye each of 18 New Zealand White rabbits. The fellow eye of each rabbit was treated with control vehicle. Blink response to a mechanical stimulus was assessed. Blink response was also assessed every 3 h for 30 h in 6 rabbits treated with 1 mM TTX administered every 6 h. In a separate group of 12 rabbits with central epithelial debridement, the rate of epithelial healing was compared between animals treated with topical 1.0 mM TTX and animals receiving no treatment.
After 4 h, eyes treated with 1.0 mM and 0.1 mM TTX were anesthetic. At 6 h, five of six rabbit eyes treated with 1.0 mM TTX were still partially anesthetic. By 8 h, the mean anesthesia score for 1.0 mM TTX was approaching normal. With multiple dosing, all six rabbit eyes remained anesthetic for the duration of the experiment. There was no significant difference in the rate of re-epithelialization between eyes treated with TTX and untreated controls. There was no evidence of systemic or local toxicity from topical TTX.
In a rabbit model, TTX is a long-acting topical anesthetic that retains its effectiveness when administered repeatedly over 24 h and does not inhibit epithelial healing. It may have application in management of pain after photorefractive keratectomy.
河豚毒素（TTX）与钠通道具有高亲和力并产生局部麻醉作用。我们研究了TTX在兔眼中是否为一种有效、长效的角膜麻醉剂。
对18只新西兰白兔的每只眼睛进行中央角膜上皮机械清创后，将局部用TTX（1 mM、0.1 mM或0.01 mM）应用于其中一只眼睛。每只兔子的另一只眼睛用对照赋形剂处理。评估对机械刺激的眨眼反应。对每6小时给予1 mM TTX治疗的6只兔子，还在30小时内每3小时评估一次眨眼反应。在另一组12只进行中央上皮清创的兔子中，比较局部用1.0 mM TTX治疗的动物与未治疗动物的上皮愈合率。
4小时后，用1.0 mM和0.1 mM TTX治疗的眼睛出现麻醉效果。6小时时，用1.0 mM TTX治疗的6只兔眼中有5只仍处于部分麻醉状态。到8小时时，1.0 mM TTX的平均麻醉评分接近正常。多次给药后，所有6只兔眼在实验期间均保持麻醉状态。用TTX治疗的眼睛与未治疗的对照眼在上皮再形成率方面无显著差异。没有证据表明局部用TTX有全身或局部毒性。
在兔模型中，TTX是一种长效局部麻醉剂，在24小时内重复给药时仍保持其有效性且不抑制上皮愈合。它可能在准分子激光原位角膜磨镶术后疼痛管理中有应用价值。
