Metabolic Cage Analysis of Surgically Catheterized C57BL/6J Mice (Mus musculus) Treated with Carprofen and Sustained-Release Buprenorphine
Federal regulations require that appropriate analgesia be provided to laboratory animals for pain control. Carprofen and buprenorphine are 2 common analgesics used for laboratory mice (Mus musculus). However, given the potential gastrointestinal side effects that these analgesics have in various species, the impact of these analgesics on mice used in metabolic studies could be concerning. To investigate the impact of carprofen and sustained-release buprenorphine on food consumption, activity level, and whole-body metabolism, we administered carprofen alone or in combination with sustained-release buprenorphine to mice that underwent jugular vein and carotid artery catheterization, or a sham surgery. The mice were individually housed in instrumented metabolic cages to continuously quantify food consumption, activity levels, and energy expenditure by indirect calorimetry. We hypothesized that catheterized mice receiving both carprofen and sustained-release buprenorphine would have decreased food consumption and increased activity level compared with mice which received sham surgery and carprofen, and that catheterized mice treated with carprofen only would have similar food consumption and activity level as sham mice which received carprofen. Our results demonstrate that during the initial 12 hours after surgery, catheterized mice that received both carprofen and sustained-release buprenorphine were more active than sham mice which received carprofen, and they were more active and consumed more food than catheterized mice which received carprofen only. Our study demonstrated that analgesia regimen can affect metabolic parameters, thus, researchers should carefully consider the effects that analgesic drugs can have on mice when designing metabolic or behavioral experiments.
Study Design and Hypothesis. Mice were subjected to baseline measurements and then were assigned to 1 of 3 treatment groups: sham surgery plus carprofen (Sham+C), catheterization surgery plus carprofen and buprenorphine (Sx+C+SRB), and catheterization surgery plus carprofen alone (Sx+C). Postsurgical data were collected and the a priori hypotheses are indicated.
Presurgery Body Weight, Food Consumption, Activity Level, and Energy Expenditure. (A–I) Prior to any treatment, body weight was measured (A), and mice were placed in instrumented metabolic cages individually to measure food consumption (B, C; in C, the light gray bars represent light periods, and the dark gray bars represent dark periods), locomotor activity (D, E), total distance traveled (F, G), and energy expenditure (H, I). Cumulative (B, D, F, H) and continuous (C, E, G, I) data are reported. Data are reported as mean ± SEM; no differences were detected between groups.
Postsurgery Body Weight and Food Consumption. Following surgery and administration of analgesics, mice were placed in metabolic cages for 72 hours. (A–G) Body weight was measured upon removal from the cages (A), and total (B) and continuous (C) food consumption were quantified (B, C); cumulative data over the first 12 (D) and 24 hours (E) are also reported, as are the change in food consumption relative to baseline data (F, G). Data are reported as mean ± SEM. *, P < 0.05.
Postsurgery Activity Level: Locomotor Activity and Total Distance Traveled in Cage. Following surgery and administration of analgesics, mice were placed in metabolic cages for 72 hours. (A–L) Instrumented metabolic caging was used to quantify total locomotor activity (A–D) and distance traveled in the cage over 72 hours (E–H); locomotor activity (I, J) and distance traveled in the cage (K, L) relative to baseline data were calculated. Data are reported as mean ± SEM. *, P < 0.05.
Postsurgery Energy Expenditure. Following surgery and administration of analgesics, mice were placed in metabolic cages for 72 hours. (A–D) Instrumented metabolic caging was used to quantify total (A) and continuous (B) energy expenditure; cumulative data over the first 12 (C) and 24 hours (D) are also reported. Data are reported as mean ± SEM. No differences were detected between groups.
Pain Scores. Total pain scores were calculated according to the rubric in Table 1. Data were recorded 6 hours after surgery and for 1, 2, and 3 days after surgery (D1, D2, and D3, respectively). Data are reported as mean ± SEM. #, P < 0.05 for Sham+C compared with Sx+C mice; $, P < 0.05 for Sham+C compared with Sx+C+SRB mice; *, P < 0.05 for Sx+C compared with Sx+C+SRB mice.
Contributor Notes
These authors contributed equally to this study.