ABSTRACT
Background and aim: Animal modelling of arthritis is often associated with pain and suffering. Severity may be reduced with the use of analgesia which is, however, often withheld due to concerns of introducing a confounding variable. It is therefore important to design and validate pain relief protocols that reduce pain without compromising the scientific objectives. The present study evaluated the effect of buprenorphine analgesia in the immediate post-induction period of an adjuvant-induced monoarthritic rat model. The aim of this study was to extend previous work on refinement of the model by alleviating unnecessary pain. Methods: Male and female Sprague Dawley rats were injected with 20 µl of complete Freund's adjuvant (CFA) into the left ankle. Rats were treated with buprenorphine, either injected subcutaneously or ingested voluntarily, and were compared to rats given subcutaneous injections with vehicle (saline or pure nut paste) or carprofen the first three days post CFA-injection. Measurements of welfare, clinical model-specific parameters and pain-related behaviour were assessed. Results: Buprenorphine, administered either subcutaneously (0.10 or 0.15 mg/kg, twice daily) or by voluntary ingestion in nut paste (1.0 or 3.0 mg/kg, twice daily), improved mobility, stance, rearing and lameness scores significantly 7 h post CFA-injection. Mechanical hyperalgesia peaked at 7 h and was significantly lower in buprenorphine-treated animals, compared to vehicle-treated animals. Joint circumference was highest 24-72 h after CFA injection. Animals treated with buprenorphine did not decrease in joint circumference, opposite carprofen treated animals. Conclusion: Buprenorphine, administered either subcutaneously or by voluntary ingestion, provides adequate analgesia for both sexes within the first 24 h post CFA-injection. Buprenorphine treatment improved clinical scores and appeared not to suppress the inflammatory response. The present study supports previous findings that voluntarily ingested buprenorphine is an effective alternative to repeated injections.
ABSTRACT
BACKGROUND: Outbred Sprague-Dawley (SD) rats are a commonly used strain in preclinical pain research. Here, we established empirically how SD rats obtained from different vendors might vary in sensitivity to injury and pharmacotherapy. METHODS: Chronic Constriction Injury (CCI) or complete Freund's adjuvant (CFA) hindpaw inflammation was induced in male SD rats sourced from three to four different vendors, respectively. Neuropathic hypersensitivity was evaluated over 58 days using von Frey filaments, pinprick stimulation and the hot plate test. Pharmacological sensitivity was evaluated by treatment with gabapentin (100 mg/kg, p.o.) or morphine (3 mg/kg, s.c.). CFA-induced hyperalgesia and sensitivity to morphine (0.3-6 mg/kg, s.c.) was measured using a digital Randall-Selitto device. In addition, paw weight gain was used as an index of peripheral oedema. RESULTS: Significant differences between the vendor-supplied SD rats in relation to onset, magnitude and resolution of hypersensitivity after CCI were observed. Although all sub-strains eventually developed a robust and reversible neuropathic hypersensitivity to mechanical stimulation, the thermal hypersensitivity varied. Whereas pharmacological response to gabapentin varied enormously, the response to morphine was both robust and much more consistent between sub-strains. Despite a similar degree of CFA-induced hypersensitivity, the paw oedema level differed between sub-strains. Here, morphine dose-dependently alleviated the CFA-induced hypersensitivity, with only a subtle difference in sensitivity between sub-strains observed. CONCLUSIONS: Our data reveal that the source of vendor used to obtain SD rats may be one key factor responsible for 'between laboratory variation' in reproducing sensitivity to some drugs targeting various pathophysiological mechanisms in specific animal pain models. SIGNIFICANCE: The choice of vendor used to source the same strain of rat for use in preclinical pain research can profoundly affect the level of nociceptive hypersensitivity and response to reference analgesics in neuropathic versus inflammatory models.
