Postoperative Analgesia Due to Sustained-Release Buprenorphine, Sustained-Release Meloxicam, and Carprofen Gel in a Model of Incisional Pain in Rats (Rattus norvegicus)

Abstract

Postoperative analgesia in laboratory rats is complicated by the frequent handling associated with common analgesic dosing requirements. Here, we evaluated sustained-release buprenorphine (Bup-SR), sustained-release meloxicam (Melox-SR), and carprofen gel (CG) as refinements for postoperative analgesia. The aim of this study was to investigate whether postoperative administration of Bup-SR, Melox-SR, or CG effectively controls behavioral mechanical and thermal hypersensitivity in a rat model of incisional pain. Rats were randomly assigned to 1 of 5 treatment groups: saline, 1 mL/kg SC BID; buprenorphine HCl (Bup HCl), 0.05 mg/kg SC BID; Bup-SR, 1.2 mg/kg SC once; Melox-SR, 4 mg/kg SC once; and CG, 2 oz PO daily. Mechanical and thermal hypersensitivity were tested daily from day-1 through 4. Bup HCl and Bup-SR attenuated mechanical and thermal hypersensitivity on days 1 through 4. Melox-SR and CG attenuated mechanical hypersensitivity-but not thermal hypersensitivity-on days 1 through 4. Plasma concentrations, measured by using UPLC with mass spectrometry, were consistent between both buprenorphine formulations. Gross pathologic examination revealed no signs of toxicity in any group. These findings suggest that postoperative administration of Bup HCl and Bup-SR-but not Melox-SR or CG-effectively attenuates mechanical and thermal hypersensitivity in a rat model of incisional pain.

Figure 1.

Daily body weight (mean ± SEM) of rats in saline, Bup HCl, Bup-SR, Melox-SR, and CG treatment groups. Arrow indicates day of surgery.

Figure 2.

Effects of saline, Bup HCl, Bup-SR, Melox-SR, and CG on mechanical hypersensitivity (mean ± SEM) of the (A) ipsilateral and (B) contralateral hindpaws. In the Bup HCl group, 0 withdrawals of the contralateral hindpaw were recorded on days 1 and 2. Arrow indicates day of surgery. *, Value significantly (P < 0.05) different from that on day –1 in the same treatment group.

Figure 3.

Effects of saline, Bup HCl, Bup-SR, Melox-SR, and CG on paw withdrawal latency (s, mean ± SEM) of (A) ipsilateral and (B) contralateral hindpaws. Arrow indicates day of surgery. *, Value significantly (P < 0.05) different from that on day –1 in the same treatment group.

Figure 4.

Plasma concentration of buprenorphine (ng/mL, mean ± SEM) in rats treated with either Bup HCl or Bup-SR (n = 3 at each time point). Plasma samples from naïve rats (n = 3) were used as negative controls for the assay.

Figure 5.

Plasma concentrations (μg/mL, mean ± SEM) of meloxicam and carprofen in rats treated with either Melox-SR or CG (n = 3 at each time point). Plasma samples from naïve rats (n = 3) were used as negative controls for the assays. *, Value significantly (P < 0.05) different from that on day –1 in the same treatment group.

Figure 6.

CG consumption (%, left) and estimated carprofen dose (mg/kg, right). Arrow indicates day of surgery. Data are presented as mean ± SEM. *, Value significantly (P < 0.05) different from that on day –2.