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.

Cutaneous Epitheliotropic T-Cell Lymphoma in a Marsh Rice Rat (Oryzomys palustris).

Published reports of spontaneous neoplasia in marsh rice rats (Oryzomys palustris) are sparse. We report here a case of cutaneous epitheliotropic T-cell lymphoma in a 14-mo-old marsh rice rat that involved the ear pinnae, with dissemination to the liver and spleen. Histologically, the thickened ear pinnae showed diffuse infiltration of neoplastic lymphocytes into the epidermis, dermis, and adnexal skin structures, with Pautrier microaggregations present in the epidermis. In addition, neoplastic lymphocytes were observed infiltrating and disrupting the architecture of the liver and spleen. Neoplastic lymphocytes were strongly positive for the T-cell marker CD3 but were negative for the B-cell markers CD19 and CD20. These histologic and immunohistochemical features are consistent with an epitheliotropic T-cell lymphoma, as previously reported in other species, including humans. To our knowledge, this report represents the first published case of spontaneous cutaneous epitheliotropic T-cell lymphoma in a marsh rice rat.

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.

Adeno-associated virus-mediated correction of a canine model of glycogen storage disease type Ia.

Glycogen storage disease type Ia (GSDIa; von Gierke disease; MIM 232200) is caused by a deficiency in glucose-6-phosphatase-alpha. Patients with GSDIa are unable to maintain glucose homeostasis and suffer from severe hypoglycemia, hepatomegaly, hyperlipidemia, hyperuricemia, and lactic acidosis. The canine model of GSDIa is naturally occurring and recapitulates almost all aspects of the human form of disease. We investigated the potential of recombinant adeno-associated virus (rAAV) vector-based therapy to treat the canine model of GSDIa. After delivery of a therapeutic rAAV2/8 vector to a 1-day-old GSDIa dog, improvement was noted as early as 2 weeks posttreatment. Correction was transient, however, and by 2 months posttreatment the rAAV2/8-treated dog could no longer sustain normal blood glucose levels after 1 hr of fasting. The same animal was then dosed with a therapeutic rAAV2/1 vector delivered via the portal vein. Two months after rAAV2/1 dosing, both blood glucose and lactate levels were normal at 4 hr postfasting. With more prolonged fasting, the dog still maintained near-normal glucose concentrations, but lactate levels were elevated by 9 hr, indicating that partial correction was achieved. Dietary glucose supplementation was discontinued starting 1 month after rAAV2/1 delivery and the dog continues to thrive with minimal laboratory abnormalities at 23 months of age (18 months after rAAV2/1 treatment). These results demonstrate that delivery of rAAV vectors can mediate significant correction of the GSDIa phenotype and that gene transfer may be a promising alternative therapy for this disease and other genetic diseases of the liver.

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.