PURPOSE: 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.
PURPOSE: 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, diltiazemdecreases pain and neurogenic inflammation and may be useful as both an analgesic and an antiinflammatory agent in the eye.
Authors: Fiona Stapleton; Carl Marfurt; Blanka Golebiowski; Mark Rosenblatt; David Bereiter; Carolyn Begley; Darlene Dartt; Juana Gallar; Carlos Belmonte; Pedram Hamrah; Mark Willcox Journal: Invest Ophthalmol Vis Sci Date: 2013-10-18 Impact factor: 4.799
Authors: Shruti Aggarwal; Ahmad Kheirkhah; Bernardo M Cavalcanti; Andrea Cruzat; Clara Colon; Emma Brown; David Borsook; Harald Prüss; Pedram Hamrah Journal: Ocul Surf Date: 2015-02-20 Impact factor: 5.033