title: Denervation of the Lacrimal Gland Leads to Corneal Hypoalgesia in a Novel Rat Model of Aqueous Dry Eye Disease.
abstract: OBJECTIVE
  Some dry eye disease (DED) patients have sensitized responses to corneal stimulation, while others experience hypoalgesia. Many patients have normal tear production, suggesting that reduced tears are not always the cause of DED sensory dysfunction. In this study, we show that disruption of lacrimal innervation can produce hypoalgesia without changing basal tear production.
  
  
  METHODS
  Injection of a saporin toxin conjugate into the extraorbital lacrimal gland of male Sprague-Dawley rats was used to disrupt cholinergic innervation to the gland. Tear production was assessed by phenol thread test. Corneal sensory responses to noxious stimuli were assessed using eye wipe behavior. Saporin DED animals were compared to animals treated with atropine to produce aqueous DED.
  
  
  RESULTS
  Cholinergic innervation and acetylcholine content of the lacrimal gland were significantly reduced in saporin DED animals, yet basal tear production was normal. Saporin DED animals demonstrated normal eye wipe responses to corneal application of capsaicin, but showed hypoalgesia to corneal menthol. Corneal nerve fiber density was normal in saporin DED animals. Atropine-treated animals had reduced tear production but normal responses to ocular stimuli.
  
  
  CONCLUSIONS
  Because only menthol responses were impaired, cold-sensitive corneal afferents appear to be selectively altered in our saporin DED model. Hypoalgesia is not due to reduced tear production, since we did not observe hypoalgesia in an atropine DED model. Corneal fiber density is unaltered in saporin DED animals, suggesting that molecular mechanisms of nociceptive signaling may be impaired. The saporin DED model will be useful for exploring the mechanism underlying corneal hypoalgesia.
authors.forename: Sue A
authors.initials: SA
authors.lastname: Aicher
authors.forename: Sam M
authors.initials: SM
authors.lastname: Hermes
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Hegarty
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D003315:Cornea / Q000187:drug effects / Q000503:physiopathology*; D003714:Denervation; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015352:Dry Eye Syndromes / Q000209:etiology* / Q000503:physiopathology; D006987:Hypesthesia / Q000209:etiology / Q000503:physiopathology; D007765:Lacrimal Apparatus / Q000294:innervation* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008610:Menthol / Q000494:pharmacology; D058748:Pain Perception; D051381:Rats; D017207:Rats, Sprague-Dawley; D013666:Tears / Q000378:metabolism
chemical_list: D008610:Menthol; D002211:Capsaicin