Tetrodotoxin: anesthetic activity in the de-epithelialized cornea.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Schwartz
D M
DM
UCSF, Department of Ophthalmology 94143, USA.
Duncan
K G
KG
Fields
H L
HL
Jones
M R
MR
D000287:Administration, Topical; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D003315:Cornea / Q000187:drug effects* / Q000503:physiopathology / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D019573:Epithelium, Corneal / Q000601:surgery; D006652:Histological Techniques; D009994:Osmolar Concentration; D011817:Rabbits; D013779:Tetrodotoxin / Q000494:pharmacology*; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects
D000777:Anesthetics; D013779:Tetrodotoxin