Effects of tramadol on immune responses and nociceptive thresholds in mice

Tramadol is a centrally acting analgesic drug with a dual mechanism of action: binding to mu-opioid receptors and potentiation of the monoaminergic systems. In this study, we evaluated the effects of the acute and chronic administration of tramadol on nociceptive thresholds (by the hot-plate test) and on immune responses (by measuring Concanavalin A-induced splenocyte proliferation, IL-2 production and natural killer activity) in the mouse. After acute subcutaneous administration, tramadol induced antinociception starting from a dose of 20 mg/kg, whereas it significantly enhanced natural killer activity and IL-2 production at doses as low as 1 mg/kg and splenocyte proliferation starting from a dose of 10 mg/kg. After the chronic administration, the antinociceptive effect of the drug was still present, whereas the immune modifications disappeared. Thus, the pharmacological profile of tramadol is totally different from that of other drugs which bind mu-opioid receptors. Our results suggest that tramadol could be a good choice for the treatment of pain in patients where immunosuppression may be particularly contraindicated.