The development of morphine tolerance and dependence is... : PAIN (original) (raw)

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The development of morphine tolerance and dependence is associated with translocation of protein kinase C

Department of Anesthesiology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA

∗Corresponding author: Dr. David J. Mayer, Department of Anesthesiology, Medical College of Virginia, P.O. Box 980516, Richmond, VA 23298-0516, USA. Tel.: (804) 786-9471; FAX: (804) 371-8300.

(Received 15 August 1994; revision received 8 December 1994; accepted 22 December 1994.)

Abstract

The development of tolerance to the analgesic effects of morphine as well as morphine dependence were greatly reduced by co-administration with morphine of GM1 ganglioside, a substance reported to block the translocation of protein kinase C (PKC) from cytosol to membrane of neurons. Rats made tolerant to intrathecal administration of morphine showed increased membrane-bound PKC in the superficial layers (laminae I and II) of the spinal cord dorsal horn but not in deeper layers. This increase was prevented by co-administration with morphine of GM1 ganglioside. These results indicate that the translocation and activation of PKC may be a critical step in the development of opiate tolerance and dependence. Modulation of PKC translocation and activation may prove useful for the management of pain and opiate addiction.