Effect of repeated topical application of clonidine cream in a rat model of postoperative pain

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Introduction: Activation of alpha2 adrenoceptors by clonidine produces analgesia. Few data are available regarding the analgesic effect of clonidine cream (CC). We, therefore, evaluated the analgesic effect of CC in a rat model of postoperative pain. Methods: CC at concentrations of 30, 100, or 300 μg/g was prepared by mixing clonidine with plastibase. A postoperative pain model was prepared in halothane–anesthetized Sprague–Dawley rats by making a 1 cm–long skin incision on the plantar hindfoot. Postoperatively, rats received topical application of plastibase, 0.1 g, or clonidine at 3, 10, or 30 μg in CC, 0.1 g, to the operated paw, once a day for 6 days, on postoperative days 0 through 5 (n=6 for each group). Mechanical allodynia and thermal hyperalgesia were quantified with paw withdrawal threshold (PWT) to mechanical stimuli and paw withdrawal latency (PWL) to heat stimuli, respectively, before and after daily CC application. Antagonizing activities of intraperitoneal yohimbine at 1 mg/kg, or atropine at 0.5 mg/kg, on effects of CC at 30 μg were also evaluated. Results: Postoperatively, PWL and PWT decreased significantly in the operated paw. Topical application of CC did not affect PWL on the operative day, but it increased PWL significantly and dose–dependently, compared with placebo, on postoperative days 1 – 4. This CC–induced increase in PWL was antagonized by yohimbine. CC did not affect PWL in the unoperated paw, and it did not affect PWT in either paw. Conclusions: These results indicate that repeated topical application of CC attenuated thermal hyperalgesia postoperatively, presumably by activating peripheral alpha2 adrenoceptors.
日本疼痛学会の論文

Effect of repeated topical application of clonidine cream in a rat model of postoperative pain

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日本疼痛学会 | 論文

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