Increased prostaglandin E2 release and activated Akt/beta-catenin signaling pathway occur after opioid withdrawal in rat spinal cord.
BACKGROUND
Prostaglandin E(2) is an important spinal modulator of nociception. However, the effects of chronic opioid administration and withdrawal on prostaglandin E(2) 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 E(2) 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 beta-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.
Dunbar
Stuart A
SA
Department of Anesthesiology, Baystate Medical Center, Springfield, Massachusetts 01199, USA. stuart.dunbar@bhs.org
Karamian
Ivan
I
Roberts
Lou
L
Zhang
Jiahui
J
D000818:Animals; D015232:Dinoprostone / Q000378:metabolism*; D008297:Male; D009020:Morphine / Q000008:administration & dosage; D009021:Morphine Dependence / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism* / Q000502:physiology
D051176:beta Catenin; D009020:Morphine; D051057:Proto-Oncogene Proteins c-akt; D015232:Dinoprostone