Increased prostaglandin E2 release and activated Akt/β-catenin signaling pathway occur after opioid withdrawal in rat spinal cord

Abstract

BACKGROUND: Prostaglandin E2 is an important spinal modulator of nociception. However, the effects of chronic opioid administration and withdrawal on prostaglandin E2 release and associated signaling pathways in the spinal cord are generally unknown. METHODS: This study sought to examine these effects using a spinal microdialysis technique in a model of chronic morphine administration and withdrawal in the rat. RESULTS: The authors found that spinal prostaglandin E2 release was unaffected by chronic morphine treatment but was significantly increased during withdrawal. Recurrent withdrawal did not further enhance this release. The authors also found up-regulation of cyclooxygenase-2 expression and phosphorylation of protein kinase Akt at Ser-473 in response to opioid withdrawal. In addition, they demonstrated that β-catenin, a transcription factor downstream of Akt, was induced during morphine withdrawal, particularly during recurrent withdrawal. CONCLUSIONS: These results suggest that opioid withdrawal activates signaling pathways associated with neuronal survival and transcriptional control, two processes implicated in neuronal development and synaptic plasticity. © 2006 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.