Analgesic Efficacy of Oral Carprofen-Treated Gel and Tablets for an Incisional Pain Model in NSG Mice
Stress in research animals affects their welfare and alters physiologic responses, potentially impacting research outcomes. Laboratory rodents often experience stress from repeated parenteral drug administrations due to handling and needle punctures. In this study, we compared the efficacy of oral carprofen tablets and carprofen-treated nutritional gels compared with injectable carprofen for alleviation of postoperative mechanical and thermal hypersensitivity in NSG mice. Male and female mice (n = 59) were randomly assigned to one of 5 groups: 1) placebo (Placebo tablets or NutraGel, daily); 2) carprofen tablets (CarpTab; 2 mg, daily); and 3) carprofen injection (Carp25SC; 25 mg/kg SC, daily), low-dose carprofen-treated gels (CarpGel-low; 0.11 mg/mL, daily); and high-dose carprofen-treated gels (CarpGel-high; 0.22 mg/mL, daily). Mechanical and thermal hypersensitivities were assessed before surgery on D-1 and at D0 (4 h), D1, and D2 afterward. Plasma carprofen concentration (n = 56) was assessed over 1 to 4 d. Daily clinical observations, fecal occult blood testing, and gross necropsies were performed. Results showed that mechanical and thermal hypersensitivity persisted in the placebo group throughout the study (D0 to D2). CarpTab and Carp25SC groups effectively attenuated mechanical hypersensitivity compared with the baseline (D0 to D2). Compared with baseline, CarpGel-low attenuated mechanical hypersensitivity on D1 and CarpGel-high attenuated mechanical hypersensitivity on D2. All carprofen treatment groups, except CarpGel-high at D0, attenuated mechanical hypersensitivity compared with placebo. Thermal hypersensitivity persisted in all carprofen treatment groups compared with baseline values. However, compared with placebo, CarpTab, Carp25SC, and CarpGel-low provided attenuation of thermal hypersensitivity. Plasma carprofen concentrations did not significantly differ among oral formulations. Fecal occult blood testing was positive only in 1 of 6 mice in the CarpGel-high group at 1 and 2 d after administration. These findings support the use of orally administered CarpTab as an alternative analgesic to Carp25SC for incisional pain in NSG mice.
(A) Carprofen medicated nutritional gel diet (0.11 mg/mL and 0.22 mg/mL; NutraGel; BioServ) and (B) oral carprofen tablets (2 mg/tablet; Rodent MDs; BioServ).
Cage setup. (A) Carprofen-medicated gel diet and (B) oral carprofen tablets were placed on small weigh boats. To prevent contamination of the gel with bedding material, cup holders were used to keep the gel elevated and contained.
Experimental timeline. (A) Hypersensitivity testing. (B) Oral carprofen plasma concentration determination. (C) Fecal occult blood testing.
Mechanical hypersensitivity of ipsilateral (surgical) hind paw: measured as the number of paw withdrawals (mean ± SEM) of left hind paw in response to mechanical stimulus. Arrow indicates surgery on D0. *, Value is significantly different (P < 0.05) when compared with baseline (D-1) value of the same treatment group. #, Value is significantly different (P < 0.05) when compared with the placebo group at a specific time point for ipsilateral (surgical) and contralateral (control) groups.
Mechanical hypersensitivity of contralateral (control) hind paw: measured as the number of paw withdrawals (mean ± SEM) of right hind paw in response to mechanical stimulus. Arrow indicates surgery on D0. *, Value is significantly different (P < 0.05) when compared with baseline (D-1) value of the same treatment group.
Thermal hypersensitivity of ipsilateral (surgical) hind paw. Thermal latency measured in seconds (mean ± SEM) was defined as the response time of the left hind paw to thermal stimulus. Arrow indicates surgery on D0. *, Value is significantly different (P < 0.05) when compared with baseline (D-1) value of the same treatment group. #, Value is significantly different (P < 0.05) when compared with the placebo group at a specific time point.
Thermal hypersensitivity of contralateral (control) hind paw. Thermal latency measured in seconds (mean ± SEM) was defined as the response time of the right hind paw to thermal stimulus. Arrow indicates surgery on D0. *, Value is significantly different (P < 0.05) when compared with baseline (D-1) value of the same treatment group. #, Value is significantly different (P < 0.05) when compared between the carprofen groups at a specific time point.
Dose of carprofen consumed (mg/kg; mean ± SEM) by NSG mice over a 4-d period.
Plasma carprofen concentrations (μg/mL; mean ± SEM) in mice (n = 3/group/time point).
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