title: Corneal sensitivity following lacrimal gland excision in the rat.
abstract: OBJECTIVE
  Dry eye disease (DED) produces ocular pain and irritation, yet a detailed characterization of ocular sensitivity in a preclinical model of DED is lacking. The aim of the present study was to assess nociceptive behaviors in an aqueous tear deficiency model of DED in the rat.
  
  
  METHODS
  Spontaneous blinking, corneal mechanical thresholds, and eye wipe behaviors elicited by hypertonic saline (5.0 M) were examined over a period of 8 weeks following the unilateral excision of either the exorbital lacrimal gland or of the exorbital and infraorbital lacrimal glands, and in sham surgery controls. The effect of topical proparacaine on spontaneous blinking and of systemic morphine (0.5-3.0 mg/kg, subcutaneous [SC]) on spontaneous blinking and eye wipe responses were also examined.
  
  
  RESULTS
  Lacrimal gland excision resulted in mechanical hypersensitivity and an increase in spontaneous blinking in the ipsilateral eye over an 8-week period that was more pronounced after infra- and exorbital gland excision. The time spent eye wiping was also enhanced in response to hypertonic saline (5.0 M) at both 1- and 8-week time-points, but only in infra- and exorbital gland excised animals. Morphine attenuated spontaneous blinking, and the response to hypertonic saline in dry eye animals and topical proparacaine application reduced spontaneous blinking down to control levels.
  
  
  CONCLUSIONS
  These results indicate that aqueous tear deficiency produces hypersensitivity in the rat cornea. In addition, the increase in spontaneous blinks and their reduction by morphine and topical anesthesia indicate the presence of persistent irritation elicited by the activation of corneal nociceptors.
authors.affiliation: Department of Biomedical Sciences College of Osteopathic Medicine, University of New England, Biddeford, Maine, United States.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Meng
authors.affiliation: Department of Biomedical Sciences College of Osteopathic Medicine, University of New England, Biddeford, Maine, United States.
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Barton
authors.affiliation: Molecular and Biomedical Sciences, University of Maine, Orono, Maine, United States.
authors.forename: Neal E
authors.initials: NE
authors.lastname: Mecum
authors.affiliation: Division of Oral Physiology, Department of Oral Biological Sciences, Niigata University, Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kurose
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001767:Blinking / Q000187:drug effects / Q000502:physiology; D003315:Cornea / Q000187:drug effects / Q000503:physiopathology*; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D005451:Fluorescein Angiography; D007765:Lacrimal Apparatus / Q000601:surgery*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D011430:Propoxycaine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012684:Sensory Thresholds / Q000502:physiology; D013666:Tears / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D000779:Anesthetics, Local; D009020:Morphine; C005717:proxymetacaine; D011430:Propoxycaine