Effects of topical application of tramadol with/without dexmedetomidine and proparacaine on corneal sensitivity in rats.

PURPOSE: To evaluate the corneal anesthetic effect following topical application of tramadol alone and in combination with dexmedetomidine, and compare it to proparacaine, in clinically healthy rats. METHODS: A randomized, crossover study was performed. Twenty Wistar albino rats (n = 40 eyes) were used. Corneal touch threshold (CTT) measurements (in mm) were obtained using a Cochet-Bonnet aesthesiometer. CTT measurements were obtained at baseline, 1-min following application of the topical anesthetic agent, and repeated at 5-min intervals up to 75 min. The topical protocol involved 3 treatment conditions, separated by a 2-week washout period: proparacaine, tramadol alone, and tramadol in combination with dexmedetomidine. RESULTS: CTT values were significantly decreased compared to baseline at each timepoint until completion of the 75-min evaluation in all treated eyes, regardless of the assigned treatment (p < 0.0083). With tramadol, complete corneal anesthesia (CTT = 0) was achieved within 1-5 min in 18 eyes and ranged from 5 to 25 min. Co-administration of dexmedetomidine to tramadol resulted in significantly increased CTT values from 5 to 20 min following topical application, compared to tramadol alone (p < 0.0083), and complete corneal anesthesia was achieved in only 14 out of 20 treated eyes. CONCLUSION: Tramadol might be a useful alternative to topical anesthetic agents, providing a dose-related corneal anesthetic effect. Co-administration of dexmedetomidine does not potentiate its anesthetic effect. The underlying mechanism(s) of drug antagonism between tramadol and dexmedetomidine remains to be determined.

Effects of topical application of 0.4% oxybuprocaine hydrochloride ophthalmic solution and 1% ropivacaine hydrochloride on corneal sensitivity in rats.

The aim of the present study was to determine and compare the degree and duration of corneal anesthesia following topical application of 0.4% oxybuprocaine hydrochloride ophthalmic solution and 1% ropivacaine hydrochloride treatment in healthy rats. A randomized, blinded, crossover study was conducted on 20 healthy adult Wistar rats, following complete physical and ophthalmological examination. Baseline corneal touch threshold (CTT) was determined in the central corneal area of both eyes with a Cochet-Bonnet aesthesiometer, in mm filament length. Oxybuprocaine was randomly applied to one eye and 0.9% sterile sodium chloride solution was instilled into the contralateral eye. Subsequent CTT measurements were performed in both eyes 5 minutes after topical application and at 5-minute intervals thereafter for 75-minutes in the anesthetized eye. Following a 2-week washout period, this protocol was repeated with ropivacaine. Quantitative data were summarized as mean ± standard deviation, median and inter-quartile range (Q1-Q3). Repeated measures data were analyzed over time and between treatments using Friedman test and Wilcoxon signed-rank test with Bonferroni adjustment (p < 0.05). Baseline CTT values were 60 mm in all eyes. With oxybuprocaine, CTT values decreased significantly for 65 minutes (0-55 mm; p = 0.002) when compared with baseline; the maximal anesthetic effect (no blink response at 5 mm filament length) was maintained for up to 15 minutes (p < 0.0001). With ropivacaine, CTT values were significantly lower than baseline for 30 minutes (0-55 mm; p = 0.002), with a maximal anesthetic effect recorded at 5 minutes in 18 eyes (p < 0.0001). Oxybuprocaine induced a significantly lower CTT than ropivacaine (p = 0.002) from 10 to 65 minutes following topical application. Both anesthetic agents induced significant corneal anesthesia; however, oxybuprocaine provided a greater and longer anesthetic effect, making it more suitable for potentially painful ophthalmologic procedures.