Role of immune processes in peripheral opioid analgesia.

The experimental data clearly demonstrate that opioids (alkaloids as well as peptides) are able to inhibit nociception arising from inflamed tissue by a local peripheral action. mu- and delta- as well as kappa-opioid receptor ligands are effective by interaction with the respective opioid receptors presumably located in the terminal region of the sensory nerves. Similar effects are obtained when endogenous opioid peptides are released under stress conditions from immune cells present in the inflamed tissue. Immunoreactive beta-EP and enkephalins, processed in these cells, seem to be the relevant peptides in this respect. Although the mechanism of stress-induced release of opioid peptides from the immunocytes is presently not clear, there is indication that this process involves cytokines and CRF. Apart from immunological processes, inflammation-induced changes also take place at the level of the opioid receptors and are of significance in the manifestation of peripheral opioid antinociception; in particular the "activation" of these receptors apparently occurs at the early stages of inflammation when the infiltration of the tissue with immunocompetent cells is just beginning. There is increasing evidence for a therapeutic relevance of opioid-induced analgesia at peripheral sites of inflammation.