Pain control in inflammation governed by selectins

Opioid-containing immune cells migrate preferentially to inflamed sites, wh ere they release beta-endorphin which activates peripheral opioid receptors to inhibit pain(1,2). Immunocyte recruitment is a multistep, sequential en gagement of various adhesion molecules located on immune cells and vascular endothelium. Selectins mediate the initial phase of immunoctye extravasati on into inflamed sites(3,4). Here we show that anti-selectin treatment abol ishes peripheral opioid analgesia elicited either endogenously (by stress) or by corticotropin-releasing factor. This results from a blockade of the i nfiltration of immunocytes containing beta-endorphin and the consequent dec rease of the beta-endorphin content in the inflamed tissue. These findings indicate that the immune system uses mechanisms of cell migration not only to fight pathogens but also to control pain in injured tissue. Thus, pain i s exacerbated by measures inhibiting the immigration of opioid-producing ce lls or, conversely, analgesia might be conveyed by adhesive interactions th at recruit those cells to injured tissue.