The Effects of Subcutaneous Ketamine on Postlaparotomy Analgesia and Behavior in Female Sprague–Dawley Rats (Rattus norvegicus)
Multimodal analgesia provides superior pain control compared with single-agent analgesic approaches. However, certain analgesic drug classes such as NSAIDs and opioids may be contraindicated in some studies due to their mechanisms of action, highlighting the need for alternative analgesic options. Little information is available as to the efficacy of alternative supplementary analgesics in laboratory rodents. Here, we investigate the impact of ketamine as an adjunctive analgesic postlaparotomy in 32 female Sprague–Dawley (SD) rats. Rats received either 4 mg/kg Meloxicam in Extended-Release Polymer (Melox-ER) or 1 mg/kg Buprenorphine Base in Extended-Release Polymer (Bup-ER), along with either ketamine (30 mg/kg SC) or volume-matched saline (n = 8 per treatment group). Postoperative pain behaviors were assessed via video scoring at 30, 90, and 150 min postoperatively, and cage-side evaluations were performed in-person at 3, 6, 12, 24, 32, 48, 56, and 72 h postoperatively. Rat grooming behavior, assessed by the grooming of fluorescent oil from the nape, was evaluated as an indirect method of assessing analgesic efficacy. All rats that received ketamine exhibited higher activity levels, reduced incisional licking, and fewer pain-associated behaviors than nonketamine-treated rats during the initial 90-min postoperative period. Rats that received Melox-ER demonstrated fewer pain-associated behaviors than Bup-ER-treated rats in the acute postsurgical period, regardless of ketamine treatment. Rats treated with Bup-ER took significantly longer to groom fluorescent oil from their fur compared with Melox-ER-treated rats. Our study demonstrates that ketamine confers significant analgesic effects for at least 90 min postoperatively and supports the use of fluorescent oil grooming transfer scores as a method for evaluating postoperative analgesia.
Pain ethogram. Ethogram criteria were used in conjunction with the rat grimace scale (RGS)64 to assess postoperative pain. A blinded observer scored each animal for each ethogram category at 3, 6, 12, 24, 32, 48, 56, and 72 h after recovery from anesthesia. The total score was calculated as the sum across all categories. Only the “Posture/Appearance” and “Behavior/Activity” components from the pain ethogram were evaluated during the retroactive video scoring assessment, as these could be readily observed via video and did not require the handler to directly interact with the animals.
Grooming transfer test scale. Intensity and spread of fluorescence were assessed under UV light for signal extinction from the dorsal neck over a 72-h period. Contrast of all images was enhanced by 10% to correct for light-balancing of photography.
Behavioral assessments of postoperative pain evaluated during retroactive video scoring for each treatment group (melox-sal, melox-ket, bup-sal, and bup-ket) in female Sprague–Dawley rats at 30, 90, and 150 min postsurgery. Shown are the cumulative frequency of (A) back-arching and writhing; (B) staggering, falling, and wobbling; scores for (C) orbital tightening; scores for (D) Posture/Appearance and (E) Behavior/Activity; and duration in seconds of (F) inactivity, (G) nonincisional grooming, and (H) licking at incision. Values are shown as mean ± SD. Significant differences between values: *, P ≤ 0.05; †, P ≤ 0.01; ‡, P ≤ 0.001; §, P ≤ 0.0001; ns, no significance.
(A) RGS and (B) pain ethogram scores for each treatment group (melox-sal, melox-ket, bup-sal, and bup-ket) evaluated cage side at 3, 6, 12, 24, 32, 48, 56, and 72 h postsurgery. Values are shown as mean ± SD. Significant differences: *, P ≤ 0.05; †, P ≤ 0.01.
Weight measured as a percentage of baseline for each treatment group (melox-sal, melox-ket, bup-sal, and bup-ket), through 72 h postsurgery. Baseline weight was measured on the morning of surgery, represented by the horizontal dashed line at 100% of baseline; symbols beneath data points represent significant differences from baseline. Values are shown as mean ± SD. Significant differences: *, P ≤ 0.05; †, P ≤ 0.01.
Neck fluorescence intensity score over 72 h postsurgery for each treatment group (melox-sal, melox-ket, bup-sal, and bup-ket) and compared with baseline. Baseline scores were collected 72 h before surgery and fully removed by rats 24 h before surgery. For both baseline and postoperative applications, fluorescent oil was applied to the nape of the neck while animals were under isoflurane anesthesia. Values are shown as mean ± SD. Significant differences between values: *, P ≤ 0.05; †, P ≤ 0.01; ‡, P ≤ 0.001; §, P ≤ 0.0001.
Mean nest-building score for each treatment group (melox-sal, melox-ket, bup-sal, and bup-ket) evaluated cage-side at 3, 6, 12, 24, 32, 48, 56, and 72 h postsurgery. Values are shown as mean ± SD; the thick and thin horizontal dashed lines represent the mean and SD of baseline nest-building scores, respectively. Symbols beneath data points represent significant differences from baseline. Significant differences between values: *, P ≤ 0.05; †, P ≤ 0.01; ‡, P ≤ 0.001; §, P ≤ 0.0001.
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