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The Scientific World Journal
Volume 2012, Article ID 940613, 9 pages
Review Article

An Emerging New Paradigm in Opioid Withdrawal: A Critical Role for Glia-Neuron Signaling in the Periaqueductal Gray

1Department of Neurology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
2Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, FL 33136, USA
3Department of Anesthesiology, State Key Laboratory of Oncology on Southern China, Cancer Center, Sun Yat-Sen University, Guangzhou 510060, China

Received 21 May 2012; Accepted 6 June 2012

Academic Editors: W. Ma and E. J. Thompson

Copyright © 2012 Handong Ouyang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The chronic use of opiates (i.e., narcotics such as the natural derivatives of opium including morphine or codeine) or opioids (i.e., semisynthetic derivatives of opium and other molecules that activate opioid receptors) induces dependence, which is associated with various specific behavioral and somatic signs after their withdrawal or after the administration of an opioid antagonist. Among the brain regions implicated in opiate dependence and withdrawal, the periaqueductal gray area (PAG) appears to be critical in regulating the complex signs and symptoms of opioid withdrawal. Numerous neurochemical mechanisms in the PAG have been identified that may contribute to the opioid withdrawal syndrome. Accumulating evidence suggests that glial activation leading to the release of proinflammatory molecules acting on neurons is important in the complex syndrome of opioid dependence and withdrawal. This paper focuses on the recent advances in our understanding of the vital role that glia-neuron interactions play in opioid dependence and withdrawal within the PAG. We summarize those neurochemical mechanisms associated with opioid withdrawal including the recently defined importance of TNFα release from activated glial cells that communicate with TNF receptors on PAG neurons.