 |
||||
|
||||
|
||||
|
||||
|
||||
Previous Article | Next Article
The Journal of Neuroscience, March 1, 2001, 21(5):1779-1786
Pronociceptive Actions of Dynorphin Maintain Chronic Neuropathic Pain
Zaijie Wang1, Luis R. Gardell1, Michael H. Ossipov1, Todd W. Vanderah1, Miles B. Brennan4, Ute Hochgeschwender5, Victor J. Hruby2, T. Phil Malan Jr1, 3, Josephine Lai1, and Frank Porreca1, 3 Departments of 1 Pharmacology, 2 Chemistry, and 3 Anesthesiology, University of Arizona Health Sciences Center, Tucson, Arizona 85724, 4 Eleanor Roosevelt Institute, Denver, Colorado 80206, and 5 Developmental Biology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104
Whereas tissue injury increases spinal dynorphin expression, the functional relevance of this upregulation to persistent pain is unknown. Here, mice lacking the prodynorphin gene were studied for sensitivity to non-noxious and noxious stimuli, before and after induction of experimental neuropathic pain. Prodynorphin knock-out (KO) mice had normal responses to acute non-noxious stimuli and a mild increased sensitivity to some noxious stimuli. After spinal nerve ligation (SNL), both wild-type (WT) and KO mice demonstrated decreased thresholds to innocuous mechanical and to noxious thermal stimuli, indicating that dynorphin is not required for initiation of neuropathic pain. However, whereas neuropathic pain was sustained in WT mice, KO mice showed a return to baselines by post-SNL day 10. In WT mice, SNL upregulated lumbar dynorphin content on day 10, but not day 2, after injury. Intrathecal dynorphin antiserum reversed neuropathic pain in WT mice at post-SNL day 10 (when dynorphin was upregulated) but not on post-SNL day 2; intrathecal MK-801 reversed SNL-pain at both times. Opioid (µ,
, and
) receptor density and G-protein activation were not different between WT and KO mice and were unchanged by SNL injury. The observations suggest (1) an early, dynorphin-independent phase of neuropathic pain and a later dynorphin-dependent stage, (2) that upregulated spinal dynorphin is pronociceptive and required for the maintenance of persistent neuropathic pain, and (3) that processes required for the initiation and the maintenance of the neuropathic pain state are distinct. Identification of mechanisms that maintain neuropathic pain appears important for strategies to treat neuropathic pain.
Key words: prodynorphin; dynorphin; neuropathic pain; opioid receptors; spinal nerve injury; nociception; gene deletion; gene knockout; transgenic; mouse
Copyright © 2001 Society for Neuroscience 0270-6474/01/2151779-08$05.00/0
This article has been cited by other articles:
Y. Xu, C. Lopes, Y. Qian, Y. Liu, L. Cheng, M. Goulding, E. E. Turner, D. Lima, and Q. Ma
Tlx1 and Tlx3 Coordinate Specification of Dorsal Horn Pain-Modulatory Peptidergic Neurons
J. Neurosci., April 9, 2008; 28(15): 4037 - 4046.
[Abstract] [Full Text] [PDF]
F. Luo, C. Yang, Y. Chen, P. Shukla, L. Tang, L. X. Wang, and Z. J. Wang
Reversal of Chronic Inflammatory Pain by Acute Inhibition of Ca2+/Calmodulin-Dependent Protein Kinase II
J. Pharmacol. Exp. Ther., April 1, 2008; 325(1): 267 - 275.
[Abstract] [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]
S. M. Geranton, C. Morenilla-Palao, and S. P. Hunt
A Role for Transcriptional Repressor Methyl-CpG-Binding Protein 2 and Plasticity-Related Gene Serum- and Glucocorticoid-Inducible Kinase 1 in the Induction of Inflammatory Pain States
J. Neurosci., June 6, 2007; 27(23): 6163 - 6173.
[Abstract] [Full Text] [PDF]
L. Tang, Y. Chen, Z. Chen, P. M. Blumberg, A. P. Kozikowski, and Z. J. Wang
Antinociceptive Pharmacology of N-(4-Chlorobenzyl)-N'-(4-hydroxy-3-iodo-5-methoxybenzyl) Thiourea, a High-Affinity Competitive Antagonist of the Transient Receptor Potential Vanilloid 1 Receptor
J. Pharmacol. Exp. Ther., May 1, 2007; 321(2): 791 - 798.
[Abstract] [Full Text] [PDF]
M. Xu, M. R. Bruchas, D. L. Ippolito, L. Gendron, and C. Chavkin
Sciatic Nerve Ligation-Induced Proliferation of Spinal Cord Astrocytes Is Mediated by {kappa} Opioid Activation of p38 Mitogen-Activated Protein Kinase
J. Neurosci., March 7, 2007; 27(10): 2570 - 2581.
[Abstract] [Full Text] [PDF]
L. Tang, P. K. Shukla, L. X. Wang, and Z. J. Wang
Reversal of Morphine Antinociceptive Tolerance and Dependence by the Acute Supraspinal Inhibition of Ca2+/Calmodulin-Dependent Protein Kinase II
J. Pharmacol. Exp. Ther., May 1, 2006; 317(2): 901 - 909.
[Abstract] [Full Text] [PDF]
Z. Marinova, V. Vukojevic, S. Surcheva, T. Yakovleva, G. Cebers, N. Pasikova, I. Usynin, L. Hugonin, W. Fang, M. Hallberg, et al.
Translocation of Dynorphin Neuropeptides across the Plasma Membrane: A PUTATIVE MECHANISM OF SIGNAL TRANSMISSION
J. Biol. Chem., July 15, 2005; 280(28): 26360 - 26370.
[Abstract] [Full Text] [PDF]
M. Terashvili, H.-e. Wu, R. J. Leitermann, H.-S. Sun, A. D. Clithero, and L. F. Tseng
Differential Mechanisms of Antianalgesia Induced by Endomorphin-1 and Endomorphin-2 in the Ventral Periaqueductal Gray of the Rat
J. Pharmacol. Exp. Ther., March 1, 2005; 312(3): 1257 - 1265.
[Abstract] [Full Text] [PDF]
R.-R. Ji and G. Strichartz
Cell Signaling and the Genesis of Neuropathic Pain
Sci. Signal., September 28, 2004; 2004(252): re14 - re14.
[Abstract] [Full Text] [PDF]
M. Xu, M. Petraschka, J. P. McLaughlin, R. E. Westenbroek, M. G. Caron, R. J. Lefkowitz, T. A. Czyzyk, J. E. Pintar, G. W. Terman, and C. Chavkin
Neuropathic Pain Activates the Endogenous {kappa} Opioid System in Mouse Spinal Cord and Induces Opioid Receptor Tolerance
J. Neurosci., May 12, 2004; 24(19): 4576 - 4584.
[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]
H.-E. Wu, H.-S. Sun, M. Darpolar, R. J. Leitermann, J. P. Kampine, and L. F. Tseng
Dynorphinergic Mechanism Mediating Endomorphin-2-Induced Antianalgesia in the Mouse Spinal Cord
J. Pharmacol. Exp. Ther., December 1, 2003; 307(3): 1135 - 1141.
[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]
M. S. Gold, D. Weinreich, C.-S. Kim, R. Wang, J. Treanor, F. Porreca, and J. Lai
Redistribution of NaV1.8 in Uninjured Axons Enables Neuropathic Pain
J. Neurosci., January 1, 2003; 23(1): 158 - 166.
[Abstract] [Full Text] [PDF]
S. E. Burgess, L. R. Gardell, M. H. Ossipov, T. P. Malan Jr, T. W. Vanderah, J. Lai, and F. Porreca
Time-Dependent Descending Facilitation from the Rostral Ventromedial Medulla Maintains, But Does Not Initiate, Neuropathic Pain
J. Neurosci., June 15, 2002; 22(12): 5129 - 5136.
[Abstract] [Full Text] [PDF]
R.-R. Ji, K. Befort, G. J. Brenner, and C. J. Woolf
ERK MAP Kinase Activation in Superficial Spinal Cord Neurons Induces Prodynorphin and NK-1 Upregulation and Contributes to Persistent Inflammatory Pain Hypersensitivity
J. Neurosci., January 15, 2002; 22(2): 478 - 485.
[Abstract] [Full Text] [PDF]
A. Zimmer, E. Valjent, M. Konig, A. M. Zimmer, P. Robledo, H. Hahn, O. Valverde, and R. Maldonado
Absence of Delta -9-Tetrahydrocannabinol Dysphoric Effects in Dynorphin-Deficient Mice
J. Neurosci., December 1, 2001; 21(23): 9499 - 9505.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|