Information on the effectiveness of a new long-lasting buprenorphine formulation, extended-release buprenorphine, in the neonatal rat is very limited. This study compares whether a high dose of extended-release buprenorphine (XR-Hi) attenuates thermal hypersensitivity for a longer period than a low dose of extended-release buprenorphine (XR-Lo) in a neonatal rat incisional pain model. Two experiments were performed. Experiment one: Male and female postnatal day-5 rat pups (n = 38) were randomly assigned to 1 of 4 treatment groups and received a subcutaneous administration of one of the following: 1) 0.9%NaCl (Saline), 0.1 mL; 2) sustained release buprenorphine (Bup-SR), 1 mg/kg; 3) XR-Lo, 0.65 mg/kg; and 4) XR-Hi, 1.3 mg/kg. Pups were anesthetized with sevoflurane in 100% O2 and a 5 mm long skin incision was made over the left lateral thigh and underlying muscle dissected. The skin was closed with surgical tissue glue. Thermal hypersensitivity testing (using a laser diode) and clinical observations were conducted 1 hour (h) prior to surgery and subsequently after 1, 4, 8, 24, 48, 72 h of treatment. Experiment two: The plasma buprenorphine concentration level was evaluated at 1, 4, 8, 24, 48, 72 h on five-day-old rat pups. Plasma buprenorphine concentration for all treatment groups remained above the clinically effective concentration of 1 ng/mL for at least 4 h in the Bup-SR group, 8 h in XR-Lo and 24 h in XR-Hi group with no abnormal clinical observations. This study demonstrates that XR-Hi did not attenuate postoperative thermal hypersensitivity for a longer period than XR-Lo in 5-day-old rats; XR-Hi attenuated postoperative thermal hypersensitivity for up to 4 h while Bup-SR and XR-Lo for at least 8 h in this model.

In this case study, 15 adult laboratory Xenopus (Silurana) tropicalis (7 adult males and 8 adult females) were examinedfor nodular enlargements of the clawed digits (digits 0, I, II, and III) on the hind feet. Radiographs showed smoothly margined,rounded, peripherally mineralized lesions arising from the distal phalanges of digits 0-III with osteoproductive and osteolytic components in all frogs. Micro computed tomography (microCT) scans further revealed interphalangeal (IP),metacarpophalangeal (MCP), and metatarsophalangeal (MTP) joint osteoarthritis characterized by periarticular new bone formation, rounded mineral foci both peripherally and centrally within the joints, and more rarely, linear mineralizationpalmar/plantar to the joints in the flexor tendons. In the nonclawed digits, the shape of the distal phalanx was variablydistorted and both subluxation and malangulation of IP joints were identified. Histologically, nodules corresponded to aperipheral rim of mature cortical bone surrounding central adipose tissue, scattered hematopoietic elements, and residualbone of the distal phalanx. Occasionally, the peripheral rim of cortical bone extended proximally to encompass the distalaspect of adjacent phalanx. MCP, MTP and IP joint spaces of most digits exhibited widespread osteoarthritis characterizedby periarticular cartilaginous or osseous metaplasia, bony remodeling, and less frequently, granulomatous osteomyelitis.Nutritional analyses of the feed did not indicate imbalances nor were the lesions consistent with metabolic bone disease.The exact etiopathogenesis of these lesions is unknown; however, we hypothesize that the osteoarthritic changes are due toa combination of the frogs’ mature age, the unique structure of the Xenopus spp. claw, genetics and biomechanical forces onthe digits and distal phalanges of the hind feet.