Clinical efficacy of buprenorphine to minimize distress in MRL/lpr mice

Abstract

MRL/MpJ-Fas(lpr) (MRL/lpr) mice are an accepted animal model to study human systemic lupus erythematosus. We tested if a commonly used analgesic (buprenorphine hydrochloride) would reduce pain and distress in these mice without impacting the progression of autoimmune disease. Female MRL/lpr mice were randomly separated into four groups. Experimental groups received cyclophosphamide (25 mg/kg i.p. weekly), buprenorphine (0.09 mg/kg/mouse/day via drinking water), or cyclophosphamide+buprenorphine from 11 to 21 weeks of age. Controls received no treatments. Mice were monitored daily by a licensed veterinarian (blinded observer) and assigned a score weekly on parameters associated with pain and distress as well as progression of disease. Proteinuria was measured weekly, and serum anti-dsDNA antibody levels were determined at 11, 15, and 18 weeks of age. At 21 weeks of age, the animals were euthanized and the kidneys and spleens were removed for evaluation. Regardless of the parameter observed, buprenorphine did not significantly decrease distress when compared to the controls. Buprenorphine did not alter the progression of autoimmune disease, based on characteristics of splenic architecture and splenocyte cell profiles, development of lymphadenopathy, or kidney histology as compared to controls. This study indicates that buprenorphine at this dose and route of administration was ineffective in reducing distress associated with disease progression in the MRL/lpr strain. More studies are needed to determine if, at a different dose or route, buprenorphine would be useful as adjunctive therapy in reducing distress in MRL/lpr mice.

Buprenorphine for pain relief in mice: repeated injections vs sustained-release depot formulation

“…Several attempts have been made to overcome these problems and assure the continuous and stress-free administration of buprenorphine analgesia in laboratory rodents. Oral administration, for example via drinking water, 19,20 medicated food pellets 21 or Nutella paste, 11,22 as well as sustained release of the drug via osmotic pumps 23 or a solvent injectable system containing the drug, have been presented recently using rats and mice. 6,24–26 These application routes appear as promising alternatives to repeated injections, and sustained-release formulations, with slow and long-lasting continuous release, promise controlled delivery and assure a therapeutically effective blood concentration of the drug.…”

Beneficial Effect ofBupleurumPolysaccharides on Autoimmune-Prone MRL-lpr Mice

“…During the physical exam, each mouse was palpated to determine the extent of lymph node enlargement that was present. Lymph node enlargement was scored as follows: 0, none; 1, mild enlargement (palpable, but not easily visible); 2, moderate enlargement (easily visible, but not interfering with mobility); and 3, severe enlargement (easily visible and interfering with mobility regardless of extent of interference) [ 13 ].…”

Osteotomy models – the current status on pain scoring and management in small rodents

“…[41][42][43][44] Different dosages have been specified for subcutaneous or intraperitoneal injection ranging between 0.05 and 0.75 mg/kg for repeated doses, respectively, [45][46][47] or for administration via drinking water (9 mg/L) for mice or via food (jelly) at 0.15 mg/kg. 48,49 There are new studies on the application interval of buprenorphine which indicate that the pharmacokinetic half-life is short (<6 h). 50 In order to avoid additional stress for the animals from regular handling during injection, non-invasive application over drinking water and food is preferable.…”