Tramadol/paracetamol treatment attenuates the development of collagen antibody-induced arthritis and interferes with prednisolone treatment in mice

Abstract

The collagen antibody-induced arthritis (CAIA) model is highly effective in inducing arthritis, making it an attractive model for screening therapeutic compounds such as glucocorticoids (GCs). The severity of discomfort in this model makes it desirable to administer analgesics, but it is a prerequisite that these do not interfere with the model or tested therapeutics. In the present study, we studied the effect of 1 mg/mL tramadol and 3.5 mg/mL paracetamol (TP) on CAIA in male BALB/cAnNCrl mice and the possible interference of TP analgesia with the activity of the GC drug prednisolone (Pred). Our results showed that TP abolished the Pred-induced amelioration of CAIA, as well as several other Pred-induced effects, such as the reduction in thymus weight and the increase in insulin level. This most likely results from the effects of TP on the hepatic metabolism of this drug, since it strongly increased the Cyp3a11 expression in the liver. Altogether, we conclude that TP analgesia is not suitable for the CAIA model in male BALB/cAnNCrl mice, in particular when evaluating the effects of GCs such as Pred.