Figure 1.

Migration of opioid-containing immune cells and opioid release within inflamed tissue. Adhesion molecules interact with their respective ligands to facilitate endothelial transmigration of immune cells. In response to stress or releasing agents (e.g., CRF, IL-1, and CXCL8), the immune cells secrete opioid peptides. Opioid peptides or exogenous opioids bind to opioid receptors on primary afferent neurons, leading to analgesia. The immune cells, depleted of opioids, then migrate to regional lymph nodes. The arrows denote an increased expression within inflamed tissue of cell adhesion molecules, opioid receptors, endogenous opioid peptides, and receptors for ligands that trigger opioid release on the surface of immune cells (e.g., CXCR2, IL-1 receptors, and CRF receptors). All these enhance the analgesic activity of the peripheral opioid pathway in inflammatory conditions. Figure adapted from Ref. (2).