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Bruce Gaynes, Michael Russo, David Goldmeier; Efficacy of a novel synthetic topical tetrapeptide on eliciting analgesia subsequent to experimentally induced chemical corneal injury. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5416.
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© ARVO (1962-2015); The Authors (2016-present)
To ascertain analgesic action of a novel synthetic tetrapeptide (SIS-ZEP04) analogue in reducing pain in a rat model of experimentally induced chemical corneal injury.
Eight adult Sprague Dawley rats were utilized for study. Following approval of the local animal use committee, animals underwent treatment with 20 µL of 0.01 mg/mL of tetrapeptide in 0.01% ethanol vehicle twice daily in the right eye for 14 consecutive days. A negative control was employed in the fellow eye. Efficacy of the peptide as an analgesic was ascertained by the capsaicin eye irritant test comprised of a dilute 0.02% solution of capsaicin. Capsaicin administration to both eyes was performed at baseline, day 7 and day 14. The time required for resolution of blepharospasm, eye wiping and squinting following administration of capsaicin was recorded as a surrogate indicator of analgesic efficacy in relation to the control eye.
Mean time (seconds) for recovery from capsaicin induced irritation in both right and left eyes at baseline was 38.0 +/- 7.8 and 52.2 +/- 9.8 seconds respectively. Following SIS-ZEP04 treatment (day 14) mean time for capsaicin induced irritation recovery was 12.75 +/-5.6 and 24.4 +/- 14.69 seconds for right and left eyes respectively. A statistically significant reduction in mean time to capsaicin recovery was found for both right and left eyes (paired one way t test, p=0.0125 and 0.0036 respectively, alpha=0.5). Cochet-Bonnet aesthesiometry measurements did not deviate from baseline levels at study conclusion.
The exogneous application of a synthetic tetrapeptide appears to demonstrate significant efficacy in reducing ocular pain and modifying pathways of nociception following experimental chemical ocular injury. As analgesic action was apparent in both treated and control eyes, it is unclear what effect, if any, the vehicle exerted in minimizing ocular pain or rather if a central action induced by systemic absorption of the peptide is in place. Moreover, the analgesic action appears to occur without reduction in corneal sensitivity. Further study is required to clarify the mechanism by which this peptide exerts apparent analgesia in the mammalian eye.
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