 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
Previous Article | Next Article
The Journal of Neuroscience, December 15, 1999, 19(24):10886-10897
Neurochemical and Cellular Reorganization of the Spinal Cord in a Murine Model of Bone Cancer Pain
Matthew J. Schwei1, 3, Prisca Honore1, 3, Scott D. Rogers1, 3, Janeen L. Salak-Johnson1, 3, Matthew P. Finke1, 3, Margaret L. Ramnaraine2, Denis R. Clohisy2, and Patrick W. Mantyh1, 3 1 Neurosystems Center and Departments of Preventive Sciences, Psychiatry, Neuroscience, and Cancer Center, and 2 Department of Orthopaedic Surgery and Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, and 3 Veterans Administration Medical Center, Minneapolis, Minnesota 55417
The cancer-related event that is most disruptive to the cancer patient's quality of life is pain. To begin to define the mechanisms that give rise to cancer pain, we examined the neurochemical changes that occur in the spinal cord and associated dorsal root ganglia in a murine model of bone cancer. Twenty-one days after intramedullary injection of osteolytic sarcoma cells into the femur, there was extensive bone destruction and invasion of the tumor into the periosteum, similar to that found in patients with osteolytic bone cancer. In the spinal cord, ipsilateral to the cancerous bone, there was a massive astrocyte hypertrophy without neuronal loss, an expression of dynorphin and c-Fos protein in neurons in the deep laminae of the dorsal horn. Additionally, normally non-noxious palpation of the bone with cancer induced behaviors indicative of pain, the internalization of the substance P receptor, and c-Fos expression in lamina I neurons. The alterations in the neurochemistry of the spinal cord and the sensitization of primary afferents were positively correlated with the extent of bone destruction and the growth of the tumor. This "neurochemical signature" of bone cancer pain appears unique when compared to changes that occur in persistent inflammatory or neuropathic pain states. Understanding the mechanisms by which the cancer cells induce this neurochemical reorganization may provide insight into peripheral factors that drive spinal cord plasticity and in the development of more effective treatments for cancer pain.
Key words: astrocyte; gliosis; nociception; primary afferents; sensitization; osteolysis
Copyright © 1999 Society for Neuroscience 0270-6474/99/192410886-12$05.00/0
This article has been cited by other articles:
A. E. Metz, H.-J. Yau, M. V. Centeno, A. V. Apkarian, and M. Martina
Morphological and functional reorganization of rat medial prefrontal cortex in neuropathic pain
PNAS, February 17, 2009; 106(7): 2423 - 2428.
[Abstract] [Full Text] [PDF]
D. T. Hamamoto, S. G. Khasabov, D. M. Cain, and D. A. Simone
Tumor-Evoked Sensitization of C Nociceptors: A Role for Endothelin
J Neurophysiol, October 1, 2008; 100(4): 2300 - 2311.
[Abstract] [Full Text] [PDF]
A. Delaney, S. M. Fleetwood-Walker, L. A. Colvin, and M. Fallon
Translational medicine: cancer pain mechanisms and management
Br. J. Anaesth., July 1, 2008; 101(1): 87 - 94.
[Abstract] [Full Text] [PDF]
C. E. Constantin, N. Mair, C. A. Sailer, M. Andratsch, Z.-Z. Xu, M. J. F. Blumer, N. Scherbakov, J. B. Davis, H. Bluethmann, R.-R. Ji, et al.
Endogenous Tumor Necrosis Factor {alpha} (TNF{alpha}) Requires TNF Receptor Type 2 to Generate Heat Hyperalgesia in a Mouse Cancer Model
J. Neurosci., May 7, 2008; 28(19): 5072 - 5081.
[Abstract] [Full Text] [PDF]
R. Benoliel, J. Epstein, E. Eliav, R. Jurevic, and S. Elad
Orofacial Pain in Cancer: Part I--Mechanisms
Journal of Dental Research, June 1, 2007; 86(6): 491 - 505.
[Abstract] [Full Text] [PDF]
K. Ogawa, T. Mukai, D. Asano, H. Kawashima, S. Kinuya, K. Shiba, K. Hashimoto, H. Mori, and H. Saji
Therapeutic Effects of a 186Re-Complex-Conjugated Bisphosphonate for the Palliation of Metastatic Bone Pain in an Animal Model
J. Nucl. Med., January 1, 2007; 48(1): 122 - 127.
[Abstract] [Full Text] [PDF]
M. J. Goblirsch, P. P. Zwolak, and D. R. Clohisy
Biology of bone cancer pain.
Clin. Cancer Res., October 15, 2006; 12(20): 6231s - 6235s.
[Abstract] [Full Text] [PDF]
K. G. Halvorson, K. Kubota, M. A. Sevcik, T. H. Lindsay, J. E. Sotillo, J. R. Ghilardi, T. J. Rosol, L. Boustany, D. L. Shelton, and P. W. Mantyh
A Blocking Antibody to Nerve Growth Factor Attenuates Skeletal Pain Induced by Prostate Tumor Cells Growing in Bone
Cancer Res., October 15, 2005; 65(20): 9426 - 9435.
[Abstract] [Full Text] [PDF]
J. R. Ghilardi, H. Rohrich, T. H. Lindsay, M. A. Sevcik, M. J. Schwei, K. Kubota, K. G. Halvorson, J. Poblete, S. R. Chaplan, A. E. Dubin, et al.
Selective Blockade of the Capsaicin Receptor TRPV1 Attenuates Bone Cancer Pain
J. Neurosci., March 23, 2005; 25(12): 3126 - 3131.
[Abstract] [Full Text] [PDF]
D. B. Carr, L. C. Goudas, E. M. Balk, R. Bloch, J. P. A. Ioannidis, and J. Lau
Evidence Report on the Treatment of Pain in Cancer Patients
J Natl Cancer Inst Monographs, July 1, 2004; 2004(32): 23 - 31.
[Abstract] [Full Text] [PDF]
C. Urch
The pathophysiology of cancer-induced bone pain: current understanding
Palliative Medicine, June 1, 2004; 18(4): 267 - 274.
[Abstract] [PDF]
M. Ramnaraine, W. Pan, M. Goblirsch, C. Lynch, V. Lewis, P. Orchard, P. Mantyh, and D. R. Clohisy
Direct and Bystander Killing of Sarcomas by Novel Cytosine Deaminase Fusion Gene
Cancer Res., October 15, 2003; 63(20): 6847 - 6854.
[Abstract] [Full Text] [PDF]
M. Beckman
The Burden of Pain on the Shoulders of Aging
Sci. Aging Knowl. Environ., December 18, 2002; 2002(50): oa1 - 1.
[Abstract] [Full Text] [PDF]
M. A. C. Sabino, J. R. Ghilardi, J. L. M. Jongen, C. P. Keyser, N. M. Luger, D. B. Mach, C. M. Peters, S. D. Rogers, M. J. Schwei, C. de Felipe, et al.
Simultaneous Reduction in Cancer Pain, Bone Destruction, and Tumor Growth by Selective Inhibition of Cyclooxygenase-2
Cancer Res., December 15, 2002; 62(24): 7343 - 7349.
[Abstract] [Full Text] [PDF]
P. W. Wacnik, L. J. Eikmeier, T. R. Ruggles, M. L. Ramnaraine, B. K. Walcheck, A. J. Beitz, and G. L. Wilcox
Functional Interactions between Tumor and Peripheral Nerve: Morphology, Algogen Identification, and Behavioral Characterization of a New Murine Model of Cancer Pain
J. Neurosci., December 1, 2001; 21(23): 9355 - 9366.
[Abstract] [Full Text] [PDF]
D. M. Cain, P. W. Wacnik, M. Turner, G. Wendelschafer-Crabb, W. R. Kennedy, G. L. Wilcox, and D. A. Simone
Functional Interactions between Tumor and Peripheral Nerve: Changes in Excitability and Morphology of Primary Afferent Fibers in a Murine Model of Cancer Pain
J. Neurosci., December 1, 2001; 21(23): 9367 - 9376.
[Abstract] [Full Text] [PDF]
T. M. Laughlin, A. A. Larson, and G. L. Wilcox
Mechanisms of Induction of Persistent Nociception by Dynorphin
J. Pharmacol. Exp. Ther., October 1, 2001; 299(1): 6 - 11.
[Abstract] [Full Text] [PDF]
T. L. Yaksh, D. M. Dirig, C. M. Conway, C. Svensson, Z. D. Luo, and P. C. Isakson
The Acute Antihyperalgesic Action of Nonsteroidal, Anti-Inflammatory Drugs and Release of Spinal Prostaglandin E2 Is Mediated by the Inhibition of Constitutive Spinal Cyclooxygenase-2 (COX-2) but not COX-1
J. Neurosci., August 15, 2001; 21(16): 5847 - 5853.
[Abstract] [Full Text] [PDF]
N. M. Luger, P. Honore, M. A. C. Sabino, M. J. Schwei, S. D. Rogers, D. B. Mach, D. R. Clohisy, and P. W. Mantyh
Osteoprotegerin Diminishes Advanced Bone Cancer Pain
Cancer Res., May 1, 2001; 61(10): 4038 - 4047.
[Abstract] [Full Text]
D. M. Cain, S. G. Khasabov, and D. A. Simone
Response Properties of Mechanoreceptors and Nociceptors in Mouse Glabrous Skin: An In Vivo Study
J Neurophysiol, April 1, 2001; 85(4): 1561 - 1574.
[Abstract] [Full Text] [PDF]
J. D. Pomonis, S. D. Rogers, C. M. Peters, J. R. Ghilardi, and P. W. Mantyh
Expression and Localization of Endothelin Receptors: Implications for the Involvement of Peripheral Glia in Nociception
J. Neurosci., February 1, 2001; 21(3): 999 - 1006.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|