Effects of indomethacin and buprenorphine analgesia on the postoperative recovery of mice

Abstract

Buprenorphine (Bup) is the most commonly used analgesic in mice, yet few objective assessments address its superiority for postsurgical recovery. In mice, IP implantation of a radiotelemetry device induces decreases in body weight (BW), food and water intake (FI, WI), core temperature (Tc), and activity levels that persist approximately 14 d in the absence of analgesia. To compare the efficacy of Bup with that of the nonsteroidal antiinflammatory drug indomethacin (Indo) for postsurgical recovery, male C57BL/6J mice were treated on the day of radiotelemetry implantation with Bup (0.3 mg/kg s.c.) or Indo (1 mg/kg s.c.) followed by treatment with Indo (1 mg/kg p.o.) on the next day (Bup-Indo versus Indo-Indo). Responses were compared between treatments in mice implanted with a radiotelemetry device and those that did not undergo surgery. Changes in BW, FI, WI, Tc, and activity were examined throughout 14 d of recovery. Indo-Indo was more efficacious in inhibiting postsurgical BW, FI, and WI reductions, compared with Bup-Indo. Bup also reduced BW and FI in the absence of surgery, indicating a nonspecific effect of this drug on these variables. Indo-Indo treatment was associated with higher activity levels during lights-on-to-lights-off transition periods compared with that observed with Bup-Indo. According to 5 objective measures of surgical recovery, our data suggest that Indo-Indo treatment is more efficacious than is Bup-Indo for postsurgical recovery of radiotelemetry-implanted mice.

Figure 1.

Photograph depicting the mini-treat used for oral administration of the vehicle and analgesic solutions. Each full treat (left side of figure) weighs 1 g with a caloric value of 3.29 kcal. Each treat was split, and 1/2 of the treat (approximately 0.5 g, right side of figure) was prepared with 70 μl of the vehicle or analgesic solution and placed on the cage floor for voluntary consumption.

Figure 2.

Changes in (A) BW, (B) FI, and (C) WI after IP implantation of a radiotelemetry device in male C57BL/6J mice receiving vehicle or analgesic treatments. The transmitter represented approximately 14% of mouse BW. Day 0 represents the day of surgery. Changes are relative to the values obtained immediately (BW) or during the 24 h (FI and WI) prior to surgery. Sample sizes are indicated in parentheses. Mice received SC injection of vehicle or analgesic on the day of surgery followed by oral dosing with vehicle or analgesic at 0900 the next day (arrows in figure). Details of the treatment groups are provided in Table 1. *, Significant (P < 0.05) difference between Indo–Indo and Bup–Indo groups; #, significant (P < 0.05) difference between SCarb–SCarb and Indo–Indo groups; †, significant (P < 0.05) difference between Dex–SCarb and Bup–Indo group.

Figure 3.

Changes in (A) BW, (B) FI, and (C) WI in male C57BL/6J mice receiving vehicle or analgesic treatments. Day 0 represents the day drug treatment started. Changes are relative to the values obtained immediately (BW) or during the 24 h (FI and WI) prior to surgery. Sample sizes are indicated in parentheses. Mice received SC injection of vehicle or analgesic on the day of surgery followed by oral dosing with vehicle or analgesic at 0900 the next day (arrows in figure). Details of the treatment groups are provided in Table 1. *, Significant (P < 0.05) difference between Indo–Indo and Bup–Indo groups; #, significant (P < 0.05) difference between SCarb–SCarb and Indo–Indo groups; †, significant (P < 0.05) difference between Dex–SCarb and Bup–Indo group.

Figure 4.

Comparison of vehicle and analgesic (Indo–Indo) effects on (A) core temperature and (B) activity of male C57BL/6J mice after IP implantation of a radiotelemetry device. The transmitter represented approximately 14% of mouse BW. Mice received SC injection of vehicle or analgesic on the day of surgery (not shown) followed by oral dosing with vehicle or analgesic at 0900 the next day (arrows in figure). Details of the treatment groups are provided in Table 1. Sample sizes are shown in parentheses. Data represent 1-h averages and are only presented through day 3 because circadian profiles did not change on subsequent days. Black horizontal bars represent the lights-off (active; 1900 to 0700) period during a 12:12-h photoperiod. *, Significant (P < 0.05) difference between groups.

Figure 5.

Comparison of vehicle and analgesic (Bup–Indo) effects on (A) core temperature and (B) activity of male C57BL/6J mice after IP implantation of a radiotelemetry device. The transmitter represented approximately 14% of mouse BW. Mice received SC injection of vehicle or analgesic on the day of surgery (not shown) followed by oral dosing with vehicle or analgesic at 0900 the next day (arrows in figure). Details of the treatment groups and dosing regimen are provided in Table 1. Sample sizes are shown in parentheses. Data represent 1-h averages and are only presented through day 3 because circadian profiles did not change on subsequent days. Black horizontal bars represent the lights-off (active; 1900 to 0700) period during a 12:12-h photoperiod. *, Significant (P < 0.05) difference between groups.

Figure 6.

Comparison of analgesic (Bup–Indo versus Indo–Indo) effects on (A) core temperature and (B) activity of male C57BL/6J mice after IP implantation of a radiotelemetry device. The transmitter represented approximately 14% of mouse BW. Data represent the treatment groups shown in Figures 4 and 5 for direct comparison. Data are only presented through day 3 because circadian profiles did not change on subsequent days. Black horizontal bars represent the lights-off (active; 1900 to 0700) period during a 12:12-h photoperiod. *, Significant (P < 0.05) difference between groups. Details of the dosing regimen are provided in Table 1.