Effect of inhibition of neuropeptidases on the pain threshold of mice and rats

The effect of the inhibition of aminopeptidase and enkephalinase A on the pain threshold of mice and rats was investigated, using bestatin and thiorphan as selective peptidase inhibitors. The results indicate that both enzymes are relevant to the catabolism of enkephalins in vivo; however, their simultaneous activation requires particular conditions. These conclusions are based on the following observations: (1) Only concomitant intracerebral treatment with both inhibitors led to an increase in the threshold of animal pain, whereas, in the presence of exogenous peptides, the concomitant injection of both inhibitors in mice elicited an analgesic response greater than the sum of the effects of each single inhibitor. (2) This response could be seen only after acute trauma; in fact, when the drugs were injected through a plastic cannula, only enkephalinase A inhibition was effective in increasing analgesia induced by exogenous peptides.