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David F. Woodward, Neil J. Poloso, Jenny W. Wang; Characterization Of A Model Of Ocular Pain/discomfort With Respect To Cyclo-oxygenase And Prostanoid Receptor Involvement. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1803.
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Cyclo-oxygenase inhibitors are frequently used to alleviate the ocular surface pain associated with surgical procedures, which implies a role for prostanoids as hyperalgesic agents. These studies were intended to extend a previously reported animal model of ocular surface pain by elucidating the pharmacological basis of the prostanoid mediated component of the response to locally applied capsacian .
The capsacian induced ocular pain model in rats was employed. All drugs and vehicle were applied to the eye in a 10μL volume. Prostanoid receptor antagonists, or vehicle, were applied as a 30min pretreatment. Capsacian was applied at a 10μg/mL concentration and the behavioral response recorded over a 10 min period. Wiping of the eye with the hind paw was monitored, eye closure was ignored since it often occurred contemporaneously.
After an initial set-up protocol of 30 min to monitor the behavioral response to ocular capsacian administration, it was clear that the response was of brief duration and the behavioral monitoring phase was reduced to 10 min. Cyclo-oxygenase inhibitors diclofenac and ketorolac, at the clinically employed dose, inhibited capsacian induced ocular surface pain/discomfort by about 50%. The activity of a series of potent and selective prostanoid receptor antagonists was examined at 0.01%, ,0.1%, and 1% concentrations. Inhibition of the capsacian induced ocular pain/discomfort response was afforded by EP1, EP4, and FP receptor antagonism by SC-51322, GW 627368, and AS-604872, respectively. Antagonists at DP1 (BW A868C) DP2/TP (TM-30089), EP2 (PFE-04418948), EP3 (L-826266) and TP (SQ 29548) receptors were inactive. Two IP antagonists were used, RO-1138452 and RO-3244019 , but only RO-324019 was active. Combination of active antagonists produced no meaningful additivity. COX-2 inhibitors were inactive.
Capsacian induced ocular pain/discomfort exhibits a distinct prostanoid mediated pharmacological component. This accounts for about half the response. The involvement of EP1, EP4, and FP receptors was apparent: each operated in a non-additive, mutually exclusive manner. IP receptor involvement is not likely, since the active IP antagonist (RO-1138452) , which exhibited activity in this model , has off-target (PAF) activity and systemic toxicity.
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