@article {Machelska5588, author = {Halina Machelska and Shaaban A. Mousa and Alexander Brack and Julia K. Schopohl and Heike L. Rittner and Michael Sch{\"a}fer and Christoph Stein}, title = {Opioid Control of Inflammatory Pain Regulated by Intercellular Adhesion Molecule-1}, volume = {22}, number = {13}, pages = {5588--5596}, year = {2002}, doi = {10.1523/JNEUROSCI.22-13-05588.2002}, publisher = {Society for Neuroscience}, abstract = {Pain can be effectively controlled by endogenous mechanisms based on neuroimmune interactions. In inflamed tissue immune cell-derived opioid peptides activate opioid receptors on peripheral sensory nerves leading to potent analgesia. This is brought about by a release of opioids from inflammatory cells after stimulation by stress or corticotropin-releasing hormone (CRH). Immunocytes migrate from the circulation to inflamed tissue in multiple steps, including their rolling, adhesion, and transmigration through the vessel wall. This is orchestrated by adhesion molecules on leukocytes and vascular endothelium. Intercellular adhesion molecule-1 [ICAM-1 (or CD54)] is expressed by endothelium and mediates adhesion and extravasation of leukocytes. The goal of this study was to show that ICAM-1 regulates the homing of opioid-producing cells and the subsequent generation of analgesia within sites of painful inflammation. This was accomplished using immunofluorescence, flow cytometry, and behavioral (paw pressure) testing. We found that ICAM-1 is upregulated on the vascular endothelium, simultaneously with an enhanced immigration of opioid-containing immune cells into inflamed paw tissue. The intravenous administration of a monoclonal antibody against ICAM-1 markedly decreased the migration of opioid-containing leukocytes and of granulocytes, monocytes{\textendash}macrophages, and T cells to the inflamed tissue. At the same time, circulating immunocytes increased in numbers, and macroscopic inflammation (hyperalgesia, paw volume, and paw temperature) remained primarily unchanged. Most importantly, peripheral opioid analgesia elicited either by cold water swim stress or by intraplantar administration of CRH was dramatically reduced. Together, these findings indicate that ICAM-1 expressed on vascular endothelium recruits immunocytes containing opioids to promote the local control of inflammatory pain.}, issn = {0270-6474}, URL = {https://www.jneurosci.org/content/22/13/5588}, eprint = {https://www.jneurosci.org/content/22/13/5588.full.pdf}, journal = {Journal of Neuroscience} }