Reduction of capsaicin-induced ocular pain and neurogenic inflammation by calcium antagonists.
OBJECTIVE
To examine whether blockade of chemosensitivity of corneal nociceptors by Ca2+ antagonists decreases pain and irritation induced by capsaicin.


METHODS
In adult rabbits, the number of lid-squeezing movements and the degree of palpebral opening, miotic response, and conjunctival vasodilation evoked by a bilateral instillation of 30 microliters of capsaicin (33 mM) were measured at different times (up to 5 hours) after the drug. Irritative responses to capsaicin in eyes pretreated with diltiazem, verapamil, or nifedipine were compared with those that received only the vehicle. Protein content in aqueous humor was also measured at the end of the experiment.


RESULTS
Diltiazem at doses of 1 to 28 mM, administered 15 minutes before the application of capsaicin, significantly decreased scratching movements, conjunctival hyperemia, closure of the eye, and elevated aqueous protein concentration induced by capsaicin; however, it did not significantly reduce miosis. Nifedipine (2.8 and 10 mM) diminished the number of scratching movements but not other inflammatory parameters, whereas verapamil (2.8 and 10 mM) was totally ineffective in attenuating ocular signs of irritation produced by capsaicin.


CONCLUSIONS
These results suggest that by lowering capsaicin-induced neural activity in nociceptive terminals, diltiazem decreases pain and neurogenic inflammation and may be useful as both an analgesic and an antiinflammatory agent in the eye.
Gonzalez
G G
GG
Department of Physiology, University of Alicante, Spain.
Garcia de la Rubia
P
P
Gallar
J
J
Belmonte
C
C
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D002211:Capsaicin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D003315:Cornea / Q000187:drug effects / Q000294:innervation*; D004110:Diltiazem / Q000008:administration & dosage / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D007634:Keratitis / Q000503:physiopathology / Q000517:prevention & control; D009443:Neuritis / Q000503:physiopathology / Q000517:prevention & control*; D009543:Nifedipine / Q000008:administration & dosage / Q000627:therapeutic use; D009619:Nociceptors / Q000187:drug effects; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control*; D011817:Rabbits; D014700:Verapamil / Q000008:administration & dosage / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002121:Calcium Channel Blockers; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D002211:Capsaicin