Numerous mediators are involved in both the control and the transmission of nociceptive messages, and several lines of research have been developed in the management of pain. Complete enkephalin- degrading enzyme inhibitors, which produce naloxone-reversible analgesia in all tests where morphine has been found to be active, remains the most promising way. CCK compounds, especially the CCKB antagonists also may be interesting drugs. Indeed, they are able to strongly potentiate the antinociceptive effects of the opioids. [dickenson, wiesenfeld-hallin et al.].