Freund's adjuvant induced polyarthritis in rats has been used extensively to study pain processes of long duration. There are limitations of this model for chronic studies of pain/arthritis since the severe systemic changes provoke ethical concerns and also affect behaviour, physiology and biochemistry. Attempts to limit adjuvant-induced arthritis by plantar injection of the inoculum have been made. In this model, however, the process evolved to produce widespread polyarthritis if followed for the 6-plus-weeks necessary for chronic studies. Therefore, although it offers the researcher a reliable limited model of inflammation and nociception at the outset, for longer studies it may have all the disadvantages of the polyarthritic rat. The purpose of the present study was to produce a limited arthritic process in rats, stable over 6 weeks and suitable for behavioural and neurochemical studies of various chronic pain treatment methods. Injection (0.05 ml) of complete adjuvant containing 300 micrograms Mycobacterium butyricum in the tibio-tarsal joint produces a predictable monoarthritis, stable clinically and behaviourly from weeks 2 through 6 post injection. As revealed by clinical observations and X-ray examinations, the arthritis produced was limited anatomically, pronounced, prolonged and stable. A marked increase in sensitivity to paw pressure was seen in the affected limb. Animals gained weight and remained active, indicating little systemic disturbance as opposed to polyarthritic rats. We propose this limited model of arthritis as a suitable alternative to the polyarthritic rat for prolonged studies.
Tricyclic antidepressants (TCAs) are used extensively to treat chronic pain in man without an adequate explanation for their activity. The purpose of the present study was to investigate this problem by testing the effect of chronic TCAs in an animal pain model: the arthritic rat. Sprague-Dawley rats with adjuvant-induced arthritis were injected daily for 4 weeks with amitriptyline (10 mg/kg) or imipramine (10 mg/kg) or saline, beginning 21 days after the induction of arthritis. Baseline evaluations were made prior to the injection series and at 4 weeks, 24 h after the last injection. Both TCAs significantly reduced 'scratching' and increased 'exploring' behaviour, without changing the response to graded foot pressure. In addition clinical signs of arthritis (ankle circumference, swelling, conjunctivitis, balanitis ...) were significantly reduced, while mobility was increased. This study shows that both amitriptyline and imipramine decrease pain behaviour and arthritis in this chronic pain model. Possible 'antiinflammatory' effects of TCAs and their eventual 'analgesic' effect will be discussed.
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