Opiate-induced hypernociception and chemokine receptors

Opiates, such as morphine, are typically employed to alleviate acute or chronic pain states. However, there are a myriad of side effects including constipation, nausea, respiratory depression, cough suppression, vomiting, sedation, addiction and tolerance. It has also been reported experimentally and clinically that exposure to opiate can elicit paradoxical pain (opiate-induced tactile hyperalgesia; OIH) in regions of the body unrelated to the initial pain complaint. Several mechanisms have been suggested to be responsible for OIH such as sensitization of peripheral nociceptors, enhanced production/release of glutamate and neuropeptides in the spinal cord, protein kinase C gamma-induced signaling, and/or enhanced descending facilitation of nociceptive pathways from the rostral ventromedial medulla; however signaling pathways known to lead to directly to OIH remain undiscovered. Recent publications from our laboratory and others have discovered a potentially important link to OIH that involves the chemokine (chemotactic cytokine), stromal-derived factor 1 (SDF1 also known as CXCL12) and its cognate receptor CXCR4. (C) 2009 Elsevier Ltd. All rights reserved.