 |
||||
|
||||
|
||||
|
||||
|
||||
The Journal of Neuroscience, April 19, 2006, 26(16):4308-4317; doi:10.1523/JNEUROSCI.0003-06.2006
Previous Article | Next Article
Development/Plasticity/Repair
Activated Microglia Contribute to the Maintenance of Chronic Pain after Spinal Cord Injury
Bryan C. Hains andStephen G. Waxman Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut 06510, and Rehabilitation Research Center, Virginia Connecticut Healthcare System, West Haven, Connecticut, 06516
Correspondence should be addressed to Dr. Stephen G. Waxman, Department of Neurology, Yale University School of Medicine, 333 Cedar Street, LCI-707, New Haven, CT 06510. Email: stephen.waxman{at}yale.edu
Traumatic spinal cord injury (SCI) results not only in motor impairment but also in chronic central pain, which can be refractory to conventional treatment approaches. It has been shown recently that in models of peripheral nerve injury, spinal cord microglia can become activated and contribute to development of pain. Considering their role in pain after peripheral injury, and because microglia are known to become activated after SCI, we tested the hypothesis that activated microglia contribute to chronic pain after SCI. In this study, adult male Sprague Dawley rats underwent T9 spinal cord contusion injury. Four weeks after injury, when lumbar dorsal horn multireceptive neurons became hyperresponsive and when behavioral nociceptive thresholds were decreased to both mechanical and thermal stimuli, intrathecal infusions of the microglial inhibitor minocycline were initiated. Electrophysiological experiments showed that minocycline rapidly attenuated hyperresponsiveness of lumbar dorsal horn neurons. Behavioral data showed that minocycline restored nociceptive thresholds, at which time spinal microglial cells assumed a quiescent morphological phenotype. Levels of phosphorylated-p38 were decreased in SCI animals receiving minocycline. Cessation of delivery of minocycline resulted in an immediate return of pain-related phenomena. These results suggest an important role for activated microglia in the maintenance of chronic central below-level pain after SCI and support the newly emerging role of non-neuronal immune cells as a contributing factor in post-SCI pain.
Key words: microglia; sensitization; dorsal horn; pain; spinal cord injury; hypersensitivity
Received Jan. 2, 2006; revised March 14, 2006; accepted March 14, 2006.
Correspondence should be addressed to Dr. Stephen G. Waxman, Department of Neurology, Yale University School of Medicine, 333 Cedar Street, LCI-707, New Haven, CT 06510. Email: stephen.waxman{at}yale.edu
This article has been cited by other articles:
M. D. Galvan, S. Luchetti, A. M. Burgos, H. X. Nguyen, M. J. Hooshmand, F. P. T. Hamers, and A. J. Anderson
Deficiency in Complement C1q Improves Histological and Functional Locomotor Outcome after Spinal Cord Injury
J. Neurosci., December 17, 2008; 28(51): 13876 - 13888.
[Abstract] [Full Text] [PDF]
A. M. Tan, S. Stamboulian, Y.-W. Chang, P. Zhao, A. B. Hains, S. G. Waxman, and B. C. Hains
Neuropathic Pain Memory Is Maintained by Rac1-Regulated Dendritic Spine Remodeling after Spinal Cord Injury
J. Neurosci., December 3, 2008; 28(49): 13173 - 13183.
[Abstract] [Full Text] [PDF]
Y. Lu, J. Zheng, L. Xiong, M. Zimmermann, and J. Yang
Spinal cord injury-induced attenuation of GABAergic inhibition in spinal dorsal horn circuits is associated with down-regulation of the chloride transporter KCC2 in rat
J. Physiol., December 1, 2008; 586(23): 5701 - 5715.
[Abstract] [Full Text] [PDF]
G. Wasner, B. B. Lee, S. Engel, and E. McLachlan
Residual spinothalamic tract pathways predict development of central pain after spinal cord injury
Brain, September 1, 2008; 131(9): 2387 - 2400.
[Abstract] [Full Text] [PDF]
A. Latremoliere, A. Mauborgne, J. Masson, S. Bourgoin, V. Kayser, M. Hamon, and M. Pohl
Differential Implication of Proinflammatory Cytokine Interleukin-6 in the Development of Cephalic versus Extracephalic Neuropathic Pain in Rats
J. Neurosci., August 20, 2008; 28(34): 8489 - 8501.
[Abstract] [Full Text] [PDF]
V. B. Lu, K. Ballanyi, W. F. Colmers, and P. A. Smith
Neuron type-specific effects of brain-derived neurotrophic factor in rat superficial dorsal horn and their relevance to 'central sensitization'
J. Physiol., October 15, 2007; 584(2): 543 - 563.
[Abstract] [Full Text] [PDF]
P. Zhao, S. G. Waxman, and B. C. Hains
Modulation of Thalamic Nociceptive Processing after Spinal Cord Injury through Remote Activation of Thalamic Microglia by Cysteine Cysteine Chemokine Ligand 21
J. Neurosci., August 15, 2007; 27(33): 8893 - 8902.
[Abstract] [Full Text] [PDF]
T. Y. Yune, J. Y. Lee, G. Y. Jung, S. J. Kim, M. H. Jiang, Y. C. Kim, Y. J. Oh, G. J. Markelonis, and T. H. Oh
Minocycline Alleviates Death of Oligodendrocytes by Inhibiting Pro-Nerve Growth Factor Production in Microglia after Spinal Cord Injury
J. Neurosci., July 18, 2007; 27(29): 7751 - 7761.
[Abstract] [Full Text] [PDF]
W. Guo, H. Wang, M. Watanabe, K. Shimizu, S. Zou, S. C. LaGraize, F. Wei, R. Dubner, and K. Ren
Glial-Cytokine-Neuronal Interactions Underlying the Mechanisms of Persistent Pain
J. Neurosci., May 30, 2007; 27(22): 6006 - 6018.
[Abstract] [Full Text] [PDF]
G. C. Daginakatte and D. H. Gutmann
Neurofibromatosis-1 (Nf1) heterozygous brain microglia elaborate paracrine factors that promote Nf1-deficient astrocyte and glioma growth
Hum. Mol. Genet., May 1, 2007; 16(9): 1098 - 1112.
[Abstract] [Full Text] [PDF]
H. Taguchi, K. Oishi, S. Sakamoto, and K. Shingu
Intrathecal betamethasone for cancer pain in the lower half of the body: a study of its analgesic efficacy and safety
Br. J. Anaesth., March 1, 2007; 98(3): 385 - 389.
[Abstract] [Full Text] [PDF]
P. Zhao, S. G. Waxman, and B. C. Hains
Extracellular Signal-Regulated Kinase-Regulated Microglia-Neuron Signaling by Prostaglandin E2 Contributes to Pain after Spinal Cord Injury
J. Neurosci., February 28, 2007; 27(9): 2357 - 2368.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|