Re-epithelialization of the rat cornea is accelerated by blockade of opioid receptors

Brain Res. 1998 Jul 6;798(1-2):254-60. doi: 10.1016/s0006-8993(98)00427-2.


A native opioid peptide, [Met5]-enkephalin, termed opioid growth factor (OGF), serves as a constitutively expressed and autocrine produced inhibitory molecule related to developing, neoplastic, renewing, and healing tissues. The present study was designed to examine the effects of interfering with opioid-receptor interaction during re-epithelialization of the cornea in the rat using both systemic injections and topical applications of the potent opioid antagonist naltrexone (NTX). A 4 mm diameter epithelial defect was made in the center of the rat cornea. NTX injected twice daily or applied as eyedrops four times daily significantly accelerated re-epithelialization compared to controls. Beginning as early as 8 h after wounding, both the systemic and topical NTX treatment groups had defects that were approximately 10% to 67% smaller than control abrasions at the time points examined. Similarly, the rate of healing for the NTX groups was 4.7- and 2.8-fold greater than controls for systemic and topical paradigms, respectively. The incidence of complete re-epithelialization in animals given systemic administration of NTX was markedly accelerated in comparison to control rats; however, differences in incidence of repair between NTX and control groups receiving topical application were not observed. These results show that native opioid peptides function in wound healing, and exert a tonically inhibitory influence at the receptor level on repair of corneal epithelial injuries.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Topical
  • Animals
  • Cornea / physiopathology*
  • Corneal Injuries*
  • Epithelium / physiopathology
  • Injections, Intraperitoneal
  • Male
  • Naltrexone / administration & dosage
  • Naltrexone / pharmacology
  • Narcotic Antagonists* / administration & dosage
  • Narcotic Antagonists* / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Wound Healing / physiology*
  • Wounds, Penetrating / physiopathology*


  • Narcotic Antagonists
  • Naltrexone