CYTOKINE-INDUCED ANTINOCICEPTION MEDIATED BY OPIOIDS RELEASED FROM IMMUNE CELLS

Immune cell-derived opioid peptides (1,2) apparently play an important role in the local inhibition of pain within inflamed tissue of animal s and humans (3,4,5). Proopiomelanocortin- and proenkephalin-mRNA's, a s well as beta-endorphin (END) and [Met]enkephalin (and small amounts of dynorphin) are detectable within inflamed subcutaneous tissue (3,6, 7). These peptides are localized in T- and B-lymphocytes, monocytes an d macrophages. Upon local administration of cytokines, inflammatory pa in can be attenuated. This effect is reversible by immunosuppression w ith cyclosporine A (CsA), by passive immunization with antibodies agai nst END, and by opioid antagonists. These findings are consistent with the notion that cytokines release END from resident immune cells, whi ch subsequently activates opioid receptors on sensory nerves (3,8,9) t o inhibit nociception.