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Annabelle Reaux-le Goazigo, Hervé PORAS, Tanja OUIMET, Christophe BAUDOUIN, Stéphane MELIK PARSADANIANTZ, Michel WURM; Dual enkephalinase inhibitor (DENKI) PL265: a novel topical treatment for ocular pain?. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5172.
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© ARVO (1962-2015); The Authors (2016-present)
The peripheral endogenous opioid system is critically involved in neuropathic and inflammatory pain. Here, we tested the antinociceptive effect of a highly specific DENKI prodrug, PL265, using experimental models of corneal pain.
Adult male C57BL/6 mice (8 weeks old) were used. Under anesthesia, a corneal scraping was performed on one eye with a trephine (1.5 mm) at day 0 (D0). Some operated animals received a drop of LPS (50 µg/2 µl) after the corneal injury and again on D3. Non-operated and operated mice were treated twice a day either with a drop of PL265 (10 mM) or with PBS (control animals) in right eye for 5 days. The ocular surface was evaluated by in vivo confocal microscopy at D5. Mechanical and chemical sensitivity were evaluated with von Frey filaments at D3 and D5 and capsaicin treatment at D5, respectively. Data were analyzed using Prism® software.
In non-operated mice (without corneal injury), topical instillation with PL265 for 5 days did not change ocular surface and mechanical sensitivity compared to PBS-treated mice. In mice with corneal injury, we observed that topical daily instillation of PL265 significantly increased mechanical threshold at D5 compared to PBS-treated mice (49.00 ± 4.58 mg versus 29.60 ± 4.43 mg, p= 0.0186; n=10 per group). In addition, the palpebral closure time induced by topical capsaicin was significantly decreased (97 versus 210 seconds, p= 0.0013; n= 10 per group) after PL265 treatment. In experiments using corneal injury plus LPS instillation, we found that topical treatment with PL265 has potent antinociceptive effects. Mice treated with PL265 exhibited an increased mechanical threshold (61.00 ± 14.70 mg versus 24.00 ± 4.00 mg, p = 0.0413; n=5 per group) at D5 and a significantly shorter palpebral closure time (70 seconds compared to 170 seconds in PBS-treated mice, p= 0.0079; n = 5 per group).
This study provides the first evidence that PL265, a highly specific DENKI prodrug, is highly effective to decrease corneal sensitivity. This prodrug appears as a promising treatment for ocular pain alleviation.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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