Morphological correlates of immune-mediated peripheral opioid analgesia

The immune system is a source of opioid peptides and plays an important role in the control of inflammatory pain. Inflammation not only increases the opioid receptor expression in DRG neurons but also enhances transport and accumulation of opioid receptors on the peripheral terminals of sensory neurons. Immune cells containing opioid peptides migrate to the inflamed tissue. This is orchestrated by adhesion molecules up-regulated on vessel endothelia and co-expressed by opioid-containing immunocytes. The peptides are secreted by stressful stimuli, CRF and cytokines and the corresponding receptors are present on opioid-expressing leukocytes. The opioids bind to their receptors localized on peripheral sensory nerves leading to pain inhibion. In the more distant future, these findings might stimulate the development of novel analgesics based on enhancing the transport and release of immune-derived opioid peptides into injured tissue.