Differentiation of peripheral and central effects of analgesic drugs.

The nonsteroidal antiphlogistic and antinociceptive agents acetylsalicylic acid, diclofenac-Na and paracetamol, and the centrally acting analgesic morphine, were tested in the isolated perfused rabbit ear. This model allows for the distinction between centrally and peripherally acting analgesic drugs. It was found that local acetylsalicylic acid, diclofenac-Na and paracetamol inhibited the pain reflexes (blood pressure change, "head-flick" response) induced by bradykinin, whereas local morphine proved to be inactive. In contrast, after systemic administration, only morphine, but not acetylsalicylic acid, diclofenac-Na and paracetamol, was active in a therapeutic dose range. Thus, the isolated rabbit ear model is useful for differentiating peripheral from central sites of action of an analgesic agent.