Abstract
Complete Freund’s adjuvant (CFA)-induced arthritis in rats is a common animal model for studying chronic inflammatory pain. However, modelling of the disease is associated with unnecessary pain and impaired animal wellbeing, particularly in the immediate post-induction phase. Few attempts have been made to counteract these adverse effects with analgesics. The present study investigated the effect of buprenorphine on animal welfare, pain-related behaviour and model-specific parameters during the disease progression in a rat model of CFA-induced monoarthritis. The aim was to reduce or eliminate unnecessary pain in this model, in order to improve animal welfare and to avoid suffering, without compromising the quality of the model. Twenty-four male Sprague Dawley rats were injected with 20 μl of CFA into the left tibio-tarsal joint to induce monoarthritis. Rats were treated with either buprenorphine or carprofen for 15 days during the disease development, and were compared to a saline-treated CFA-injected group or a negative control group. Measurements of welfare, pain-related behaviour and clinical model-specific parameters were collected. The study was terminated after 3 weeks, ending with a histopathologic analysis. Regardless of treatment, CFA-injected rats displayed mechanical hyperalgesia and developed severe histopathological changes associated with arthritis. However, no severe effects on general welfare were found at any time. Buprenorphine treatment reduced facial pain expression scores, improved mobility, stance and lameness scores and it did not supress the CFA-induced ankle swelling, contrary to carprofen. Although buprenorphine failed to demonstrate a robust analgesic effect on the mechanical hyperalgesia in this study, it did not interfere with the development of the intended pathology.
Highlights
Animal models of arthritis have been used extensively for decades to understand the mechanisms of inflammatory arthritis and to screen for new therapeutic agents
Kruskal-Wallis tests detected significant higher scores in Complete Freund’s adjuvant (CFA) + BUP compared to CFA + CAR day 2 (H (3) = 6.848, p = 0.0326) and day 12 (H (3) = 9.840, p = 0.0073) but did not differ from the CFA group
Mild porphyrin staining around eyes and nose was the most numerous indicator of impaired wellbeing in all CFA-injected animals
Summary
Animal models of arthritis have been used extensively for decades to understand the mechanisms of inflammatory arthritis and to screen for new therapeutic agents. Effects of buprenorphine on adjuvant-induced monoarthritis have the potential to provide important human benefits, experimental work with models of painful conditions are problematic from a welfare point of view [1]. The primary concern with using analgesia in experimental pain models is the risk of the analgesics confounding the disease model [3]. If we wish to compromise neither animal welfare nor model validity, it is imperative to identify appropriate analgesic regimens that limit unnecessary pain, with minimal impact on the disease progression
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