Lipid bound extended release buprenorphine (high and low doses) and sustained release buprenorphine effectively attenuate post‐operative hypersensitivity in an incisional pain model in mice (Mus musculus)

BACKGROUND: Extended‐release buprenorphine (XR) is indicated for pain management in rodents, but little is known about its use in mice. This study aimed to investigate whether high dose XR effectively attenuates post‐operative hypersensitivity better than low dose XR in a mouse model of incisional pain. METHODS: Mice (n = 44) were randomly assigned to 1 of 4 treatment groups: (a) saline (1 ml/kg SC, once); (b) sustained release buprenorphine (Bup‐SR, 1 mg/kg SC, once); (c) low dose extended‐release buprenorphine (XR‐lo, 3.25 mg/kg SC, once); (d) high dose extended‐release buprenorphine (XR‐hi, 6.5 mg/kg SC, once). On days −1, 0 (4 hours), 1, 2, and 3, mechanical and thermal hypersensitivities were evaluated, and plasma buprenorphine concentrations were measured. RESULTS: Mechanical (days 0‐2) and thermal (days 0‐1) hypersensitivities were observed in the saline group. Bup‐SR, XR‐lo, and XR‐hi attenuated mechanical hypersensitivity on days 0, 1, and 2. None of the treatment groups, except XR‐Lo on day 0, attenuated thermal hypersensitivity on days 0 or 1. Plasma buprenorphine concentration peaked at 4 hours (day 0) in all treatment groups and remained greater than 1 ng/mL on days 0‐2. No abnormal clinical observations or gross pathologic findings were seen in any groups. CONCLUSION: The results indicate XR‐hi did not effectively attenuate post‐operative hypersensitivity better than XR‐lo. Thus both 3.25 and 6.5 mg/kg XR are recommended for attenuating post‐operative hypersensitivity for at least up to 48 hours in mice.