Mechanisms of Expression and Release of Endogenous Opioids in Peripheral Tissues

The topic of this review is the current understanding of the mechanisms of neuro-immune interactions responsible for suppression of pain by endogenous opioids. Special attention is paid to the events occurring in peripheral tissues after injury, excitation of high-threshold afferent inputs, and generation of nociceptive impulsation. The release of opioid peptides from immune cells migrating to the focus of inflammation and “inhabiting” the latter provides (at least partially) significant reduction of the excitability of nociceptive sensory neurons. Exogenous opioid ligands that do not cross the bloodbrain barrier also selectively modulate the excitability of primary afferents. Thus, sensory neurons in the peripheral tissues are an essential target for the action of endogenous opioids. There are reasons to believe that the clinical use of peripherally acting opioids can help one to substantially avoid the negative side effects caused by the action of conventional analgesics (opioids and anticonvulsants). Modern concepts on the mechanisms of secretion and release of peripherally acting opioids and their effects on inflammation and pain, the role of the immune response in antinociception, and prospects for the use of the above opioids in the treatment of pain-related phenomena are discussed.