Ge, Y., Alamaw, E. D., Ray, R. R. et al. 2025. Analgesic efficacy of a long-acting transdermal buprenorphine in rats (Rattus norvegicus) (2025)

Ge, Y., Alamaw, E. D., Ray, R. R. et al.

Abstract

Zorbium is the first long-acting transdermal buprenorphine (LAT-bup) approved by the FDA for relieving postoperative pain in cats for 72 h. This study aimed to investigate LAT-bup’s efficacy for attenuating postoperative mechanical and thermal hypersensitivity in a rat incisional pain model. We hypothesized that a high dose of LAT-bup would attenuate mechanical and thermal hypersensitivities more effectively than a low dose in rats for 96 h postoperatively. Two experiments were conducted. In experiment 1, a total of 34 Sprague–Dawley rats were randomly assigned into one of 4 treatment groups: (1) saline (0.9% NaCl, 5 mL/kg, transdermal); (2) buprenorphine extended-release (Bup-ER; 1.2 mg/kg, SC); (3) low-dose long-acting transdermal buprenorphine (LAT-bup low; 5 mg/kg, transdermal); or (4) high-dose long-acting transdermal buprenorphine (LAT-bup high; 10 mg/kg, transdermal). One hour after drug application, a 1-cm incision was made on the left plantar paw of the rat under isoflurane anesthesia. Mechanical and thermal hypersensitivity were measured at −24 h (24 h before surgery) and at 4, 24, 48, 72, and 96 h postsurgery. In experiment 2, 49 rats were used to measure plasma buprenorphine levels at various time points: 20 and 40 min and 1, 4, 24, 48, 72, and 96 h. Clinical observations were recorded daily, and a gross necropsy was performed at 96 h. Bup-ER and high-dose LAT-bup effectively reduced mechanical hypersensitivity from 4 to 48 h. However, neither the low nor high doses of LAT-bup attenuated thermal hypersensitivity. Plasma buprenorphine concentrations remained above 1 ng/mL from 4 to 96 h across all groups. This study demonstrates that high-dose LAT-bup attenuated postoperative mechanical hypersensitivity as effectively as Bup-ER for up to 48 h in this rat incisional pain model. Based on these findings, we recommend LAT-bup at 10 mg/kg for minor incisional pain procedures in rats.