 |
||||
|
||||
|
||||
|
||||
|
||||
Previous Article | Next Article
The Journal of Neuroscience, August 1, 2002, 22(15):6747-6755
Sustained Morphine Exposure Induces a Spinal Dynorphin-Dependent Enhancement of Excitatory Transmitter Release from Primary Afferent Fibers
Luis R. Gardell, Ruizhong Wang, Shannon E. Burgess, Michael H. Ossipov, Todd W. Vanderah, T. Philip Malan Jr, Josephine Lai, and Frank Porreca Departments of Pharmacology and Anesthesiology, University of Arizona, Tucson, Arizona 85724
Paradoxical opioid-induced pain has been demonstrated repeatedly in humans and animals. The mechanisms of such pain are unknown but may relate to opioid-induced activation of descending pain facilitatory systems and enhanced expression and pronociceptive actions of spinal dynorphin. Here, the possibility that these opioid-induced central changes might mediate increased excitability to the spinal cord was tested. Tactile and thermal hypersensitivity was observed at 7, but not 1, days after subcutaneous morphine pellet implantation; placebo pellets produced no effects. Basal and capsaicin-evoked release of calcitonin gene-related peptide (CGRP) was measured in minced spinal tissues taken from naive rats or rats on post-pellet days 1 and 7. The content and evoked release of CGRP were significantly increased in tissues from morphine-exposed rats at 7, but not 1, days after implantation. Morphine increased spinal dynorphin content on day 7 in rats with sham bilateral lesions of the dorsolateral funiculus (DLF) but not in rats with DLF lesions. Pharmacological application of dynorphin A(2-13), a non-opioid fragment, to tissues from naive rats enhanced the evoked release of CGRP. Enhanced evoked release of CGRP from morphine-pelleted rats was blocked by dynorphin antiserum or by previous lesions of the DLF. Sustained morphine induces plasticity in both primary afferents and spinal cord, including increased CGRP and dynorphin content. Morphine-induced elevation of spinal dynorphin content depends on descending influences and enhances stimulated CGRP release. Enhanced transmitter release may allow increased stimulus-evoked spinal excitation, which is likely to be critical for opioid-induced paradoxical pain. Such pain may manifest behaviorally as antinociceptive tolerance.
Key words: opiate tolerance; opioid paradoxical pain; descending facilitation; spinal dynorphin; CGRP release; opioid trophic effects
Copyright © 2002 Society for Neuroscience 0270-6474/02/22156747-09$05.00/0
This article has been cited by other articles:
R. Drdla, M. Gassner, E. Gingl, and J. Sandkuhler
Induction of Synaptic Long-Term Potentiation After Opioid Withdrawal
Science, July 10, 2009; 325(5937): 207 - 210.
[Abstract] [Full Text] [PDF]
T. Engelhardt, C. Zaarour, B. Naser, C. Pehora, J. de Ruiter, A. Howard, and M. W. Crawford
Intraoperative Low-Dose Ketamine Does Not Prevent a Remifentanil-Induced Increase in Morphine Requirement After Pediatric Scoliosis Surgery
Anesth. Analg., October 1, 2008; 107(4): 1170 - 1175.
[Abstract] [Full Text] [PDF]
L. A. Grande, B. R. O'Donnell, D. R. Fitzgibbon, and G. W. Terman
Ultra-Low Dose Ketamine and Memantine Treatment for Pain in an Opioid-Tolerant Oncology Patient
Anesth. Analg., October 1, 2008; 107(4): 1380 - 1383.
[Abstract] [Full Text] [PDF]
Y. Chen, C. Geis, and C. Sommer
Activation of TRPV1 Contributes to Morphine Tolerance: Involvement of the Mitogen-Activated Protein Kinase Signaling Pathway
J. Neurosci., May 28, 2008; 28(22): 5836 - 5845.
[Abstract] [Full Text] [PDF]
M. P. Davis, L. A. Shaiova, and M. S. Angst
When Opioids Cause Pain
J. Clin. Oncol., October 1, 2007; 25(28): 4497 - 4498.
[Full Text] [PDF]
M. H. Ossipov, I. Bazov, L. R. Gardell, J. Kowal, T. Yakovleva, I. Usynin, T. J. Ekstrom, F. Porreca, and G. Bakalkin
Control of Chronic Pain by the Ubiquitin Proteasome System in the Spinal Cord
J. Neurosci., August 1, 2007; 27(31): 8226 - 8237.
[Abstract] [Full Text] [PDF]
M. W. Crawford, C. Hickey, C. Zaarour, A. Howard, and B. Naser
Development of acute opioid tolerance during infusion of remifentanil for pediatric scoliosis surgery.
Anesth. Analg., June 1, 2006; 102(6): 1662 - 1667.
[Abstract] [Full Text] [PDF]
A. Dogrul, E. J. Bilsky, M. H. Ossipov, J. Lai, and F. Porreca
Spinal L-Type Calcium Channel Blockade Abolishes Opioid-Induced Sensory Hypersensitivity and Antinociceptive Tolerance
Anesth. Analg., December 1, 2005; 101(6): 1730 - 1735.
[Abstract] [Full Text] [PDF]
M. M. Heinricher and M. J. Neubert
Neural Basis for the Hyperalgesic Action of Cholecystokinin in the Rostral Ventromedial Medulla
J Neurophysiol, October 1, 2004; 92(4): 1982 - 1989.
[Abstract] [Full Text] [PDF]
L. Koetzner, X.-Y. Hua, J. Lai, F. Porreca, and T. Yaksh
Nonopioid Actions of Intrathecal Dynorphin Evoke Spinal Excitatory Amino Acid and Prostaglandin E2 Release Mediated by Cyclooxygenase-1 and -2
J. Neurosci., February 11, 2004; 24(6): 1451 - 1458.
[Abstract] [Full Text] [PDF]
L. R. Gardell, T. W. Vanderah, S. E. Gardell, R. Wang, M. H. Ossipov, J. Lai, and F. Porreca
Enhanced Evoked Excitatory Transmitter Release in Experimental Neuropathy Requires Descending Facilitation
J. Neurosci., September 10, 2003; 23(23): 8370 - 8379.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|