title: Corneal Anesthesia With Site 1 Sodium Channel Blockers and Dexmedetomidine.
abstract: OBJECTIVE
  Amino-amide or amino-ester local anesthetics, which are currently used for topical ocular anesthesia, are short acting and may delay corneal healing with long-term use. In contrast, site 1 sodium channel blockers (S1SCBs) are potent local anesthetics with minimal adverse tissue reaction. In this study, we examined topical local anesthesia with two S1SCBs, tetrodotoxin (TTX) or saxitoxin (STX) individually or in combination with α2-adrenergic receptor agonists (dexmedetomidine or clonidine), and compared them with the amino-ester ocular anesthetic proparacaine. The effect of test solutions on corneal healing was also studied.
  
  
  METHODS
  Solutions of TTX ± dexmedetomidine, TTX ± clonidine, STX ± dexmedetomidine, dexmedetomidine, or proparacaine were applied to the rat cornea. Tactile sensitivity was measured by recording the blink response to probing of the cornea with a Cochet-Bonnet esthesiometer. The duration of corneal anesthesia was calculated. Cytotoxicity from anesthetic solutions was measured in vitro. The effect on corneal healing was measured in vivo after corneal debridement followed by repeated drug administration.
  
  
  RESULTS
  Addition of dexmedetomidine to TTX or STX significantly prolonged corneal anesthesia beyond that of either drug alone, whereas clonidine did not. Tetrodotoxin or STX coadministered with dexmedetomidine resulted in two to three times longer corneal anesthesia than did proparacaine. S1SCB-dexmedetomidine formulations were not cytotoxic. Corneal healing was not delayed significantly by any of the test solutions.
  
  
  CONCLUSIONS
  Coadministration of S1SCBs with dexmedetomidine provided prolonged corneal anesthesia without delaying corneal wound healing. Such formulations may be useful for the management of acute surgical and nonsurgical corneal pain.
authors.affiliation: Department of Medicine Division of Medicine Critical Care, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts, United States 2Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Med.
authors.forename: James Brian
authors.initials: JB
authors.lastname: McAlvin
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts, United States.
authors.forename: Changyou
authors.initials: C
authors.lastname: Zhan
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts, United States.
authors.forename: Jenny C
authors.initials: JC
authors.lastname: Dohlman
authors.affiliation: Department of Ophthalmology, Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Paraskevi E
authors.initials: PE
authors.lastname: Kolovou
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts, United States 3Department of Ophthalmology, Schepens Eye Research I.
authors.forename: Borja
authors.initials: B
authors.lastname: Salvador-Culla
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts, United States.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Kohane
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D000772:Anesthesia, Local / Q000379:methods*; D019162:Anesthetics, Combined / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003000:Clonidine / Q000494:pharmacology*; D003315:Cornea / Q000166:cytology / Q000187:drug effects*; D020927:Dexmedetomidine / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012530:Saxitoxin / Q000494:pharmacology*; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology*
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D019162:Anesthetics, Combined; D026941:Sodium Channel Blockers; D012530:Saxitoxin; D013779:Tetrodotoxin; D020927:Dexmedetomidine; D003000:Clonidine