Analgesic Activity of Tramadol and Buprenorphine after Voluntary Ingestion by Rats (Rattus norvegicus).

Effective pain management for rats and mice is crucial due to the continuing increase in the use of these species in biomedical research. Here we used a recently validated operant orofacial pain assay to determine dose-response curves for buprenorphine and tramadol when mixed in nut paste and administered to male and female rats. Statistically significant analgesic doses of tramadol in nut paste included doses of 20, 30, and 40 mg/kg for female rats but only 40 mg/kg for male rats. For male rats receiving buprenorphine mixed in nut paste, a significant analgesic response was observed at 0.5 and 0.6 mg/kg. None of the doses tested produced a significant analgesic response in female rats. Our results indicate that at the doses tested, tramadol and buprenorphine produced an analgesic response in male rats. In female rats, tramadol shows a higher analgesic effect than buprenorphine. The analgesic effects observed 60 min after administration of the statistically significant oral doses of both drugs were similar to the analgesic effects of 0.03 mg/kg subcutaneous buprenorphine 30 min after administration. The method of voluntary ingestion could be effective, is easy to use, and would minimize stress to the rats during the immediate postoperative period.

Effect of a short-term fast on ketamine-xylazine anesthesia in rats.

Although ketamine-xylazine (KX) anesthesia is commonly used in rats, it is often reported to have an inconsistent anesthetic effect, with a prolonged induction time, an inadequate anesthetic plane, or a very short sleep time. Blood flow to the liver is known to shift after a meal in rats, perhaps explaining anesthetic variability among rats with variable prandial status. The current study tested the hypothesis that a short period of fasting (3 h) prior to induction with intraperitoneal KX anesthesia would provide a shorter time to recumbency, a longer total sleep time, and a more consistent loss of toe pinch response than would fed rats. Two groups of male Sprague-Dawley rats were used in blinded, crossover experiments. KX anesthesia was administered at 2 different doses (50 mg/kg-5 mg/kg and 70 mg/kg-7 mg/kg) after ad libitum feeding or a 3-h fast. There were no significant differences between groups in induction time, total sleep time, or loss of toe pinch response. We conclude that fasting rats for 3 h prior to KX intraperitoneal anesthesia does not affect induction time, total sleep time, loss of toe pinch response or reduce KX anesthetic variability in male Sprague-Dawley rats.

A model for clinical evaluation of perioperative analgesia in rabbits (Oryctolagus cuniculus).

Assessment of pain in rabbits is challenging, and studies of effective surgical analgesia are lacking for this species. Seeking potential indicators of postoperative pain, we performed ovariohysterectomy and telemeter placement as a form of moderate surgical injury in 20 female rabbits. Rabbits were assigned to 1 of 4 treatment groups (5 per group): buprenorphine (0.02 mg/kg SC every 12 h for 3 d); fentanyl (25-µg patch placed 24 h preoperatively); ketoprofen (1 mg/kg SC every 24 h for 3 d), and control (no treatment given). Various physiologic and behavioral variables were recorded by blinded observers, including food and water consumption, fecal output, and remotely recorded behaviors during daily exercise in 1.2 × 1.8 m floor pens. Compared with preoperative values, significant declines occurred in: food consumption (days 1 to 7), water consumption (days 1 to 4), fecal output (days 1 to 2), mean travel distance, and rearing (days 1 to 3 and day 7). No single treatment proved significantly better than another. Our results demonstrate substantial inappetance and reduction of normal activity levels in rabbits after surgery. Although results from rabbits treated with empirical doses (those typically recommended) of analgesics did not appear substantially better than those from the untreated control group, comparison of other doses and multimodal analgesic techniques by using these behavioral monitoring strategies may prove useful in future studies aimed at optimizing postoperative analgesia in rabbits.