Reduction of arthritis and pain behaviour following chronic administration of amitriptyline or imipramine in rats with adjuvant-induced arthritis.

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.