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Clinical efficacy of buprenorphine to minimize distress in MRL/lpr mice
Julie Swenson1, Selen Olgun, Ali Radjavi
1Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, United States.
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.
Insights
Buprenorphine did not reduce pain or distress in MRL/lpr mice, a model for lupus. The analgesic also did not affect the autoimmune disease progression in these mice.
Area of Science:
- Immunology
- Pharmacology
- Animal Models
Background:
- MRL/MpJ-Fas(lpr) (MRL/lpr) mice are a key model for studying human systemic lupus erythematosus.
- Assessing pain and distress management is crucial in animal models of autoimmune disease.
Purpose of the Study:
- To evaluate the efficacy of buprenorphine hydrochloride in alleviating pain and distress in MRL/lpr mice.
- To determine if buprenorphine impacts the progression of autoimmune disease in this model.
Main Methods:
- Female MRL/lpr mice were divided into four groups: control, cyclophosphamide, buprenorphine, and cyclophosphamide+buprenorphine.
- Mice were monitored for pain/distress and disease progression indicators, including proteinuria and anti-dsDNA antibody levels.
- Kidney and spleen tissues were analyzed at 21 weeks of age.
Main Results:
- Buprenorphine administration did not significantly reduce observed distress compared to control groups.
- The drug did not alter key indicators of autoimmune disease progression, such as splenic architecture, splenocyte profiles, lymphadenopathy, or kidney histology.
- Proteinuria and anti-dsDNA antibody levels remained unaffected by buprenorphine treatment.
Conclusions:
- Buprenorphine, at the tested dose and administration route, was ineffective in reducing distress in MRL/lpr mice.
- Further research is needed to explore different dosages or administration routes for buprenorphine as a potential adjunctive therapy for distress in this lupus model.

