Liposome-encapsulated oxymorphone provides prolonged relief of post-surgical visceral pain in rats |
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| Authors: | LJ Smith L Krugner-Higby M Clark D Ney E Dahly |
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| Institution: | University of Wisconsin, Madison, WI, USA |
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| Abstract: | A delayed‐release formulation of liposome‐encapsulated oxymorphone was produced using a novel dehydration–rehydration technique. The purpose of this study was to (i) compare the analgesic properties of this preparation with those of repeated injections of standard oxymorphone in rats with post‐operative visceral pain and (ii) determine whether liposome‐encapsulated oxymorphone differed from standard oxymorphone in duration of the effect. Visceral pain was elicited in approximately 300 g Sprague–Dawley rats by intestinal resection performed under isoflurane anesthesia. Rats were monitored with pulse oximetry; mean anesthesia time (35 ± 10 minutes) did not differ between the groups. Rats were randomly divided into two groups: Group 1 received 1.2 mg kg?1 liposome‐encapsulated oxymorphone SC once at skin closure and 0.2 mL of saline SC every 4 hours; Group 2 received 0.2 mL liposome‐encapsulated sucrose SC once at skin closure and 0.3 mg kg?1 standard oxymorphone SC every 4 hours. In both groups, a behavioral ethogram for pain score (grooming, porphyrin staining, body position) was recorded every 4 hours for 48 hours after surgery. Observers were blinded to the treatment. Body weight, food consumption, and urine output were recorded daily for 7 days after anesthetic recovery. Data were analyzed using anova , with significance at p < 0.05. Based on the behavioral pain score, a single injection of liposome‐encapsulated oxymorphone was as effective for relief of post‐surgical visceral pain in rats as multiple (every 4 hours) injections of standard oxymorphone administered over a 48 hour period (p = 0.18). In rats, given one dose of liposome‐encapsulated oxymorphone, the mean body weight change from day 0 to day 7 was +9.4 g, whereas rats given multiple injections of standard oxymorphone had a mean body weight change of ?3.6 g over this time (p < 0.01). Mean daily food consumption was significantly less in rats given multiple injections of standard oxymorphone (p < 0.05). There was no difference between groups in urine production. In conclusion, a single dose of liposome‐encapsulated oxymorphone was effective in treating visceral pain in rats. Rats treated with liposome‐encapsulated oxymorphone had improved recovery, based on body weight changes and food consumption, compared with rats treated with multiple doses of standard oxymorphone. Liposome‐encapsulated oxymorphone offered advantages including provision of effective analgesia, prolonged dosing intervals, and minimal handling stress. |
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