Research papersMethionine-enkephalin-and Dynorphin A-release from immune cells and control of inflammatory painCabot, Peter J.a,b,d,*; Carter, Laurendaa,b; Schäfer, Michaela,b,c; Stein, Christopha,b,cAuthor Information aBehavioral Pharmacology and Genetics Section, Intramural Research Program, NIDA/NIH, Baltimore, MD 21224, USA bDepartment of Anesthesiology and Critical Care Medicine, The Johns Hopkins University, Baltimore, MD 21287-8711, USA cKlinik für Anaesthesiologie und Operative Intensivmedizin, Klinikum Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, D12200 Berlin, Germany dSchool of Pharmacy, The University of Queensland, St Lucia, Queensland, Australia 4072 *Corresponding author. Tel.: +61-7-3365-1376; fax: +61-7-3365-1688 E-mail: [email protected] Submitted April 21, 2000; revised February 26, 2001; accepted March 29, 2001. Pain: September 2001 - Volume 93 - Issue 3 - p 207-212 doi: 10.1016/S0304-3959(01)00322-0 Buy Metrics Abstract We have previously shown that β-endorphin (END) is contained and released from memory-type T-cells within inflamed tissue and that it is capable to control pain (J Clin Invest 100(1) (1997) 142). Methionine-enkephalin (MET) and Dynorphin-A (DYN) are endogenous opioids with preference for δ- and κ-opioid receptors, respectively. Both MET and DYN are produced and contained within immune cells. The goal of this study was to determine the release characteristics of MET and DYN in a rat model of localized hindpaw inflammation and to examine the antinociceptive role of MET and DYN in a Freund's adjuvant induced model of inflammatory pain. We found that corticotropin-releasing factor (CRF) can stimulate the release of both MET and DYN from lymphocytes. This release is dose-dependent and reversible by the selective CRF antagonist α-helical-CRF. Furthermore, CRF (1.5 ng) produces analgesia when injected into the inflamed paw, which is reversible by direct co-administration of antibodies to MET. Lymphocyte content of MET was 7.0±1.4 ng/million cells, whilst DYN content was ˜30-fold lower. Both END and DYN, but not MET, were released by IL-1. Consistently, IL-1 produced peripheral analgesic effects which were not reversed by antibodies to MET. These results indicate that both MET and DYN play a role in peripheral analgesia but have different characteristics of release. These studies further support a role of the immune system in the control of inflammatory pain. This may be particularly important in patients suffering from compromised immune systems as with cancer and AIDS. © 2001 Lippincott Williams & Wilkins, Inc.