QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, December 3, 2008, 28(49):13173-13183; doi:10.1523/JNEUROSCI.3142-08.2008

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Tan, A. M. Articles by Hains, B. C. Search for Related Content PubMed PubMed Citation Articles by Tan, A. M. Articles by Hains, B. C.

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
Neuropathic Pain Memory Is Maintained by Rac1-Regulated Dendritic Spine Remodeling after Spinal Cord Injury

Andrew M. Tan,^1,3,4 Severine Stamboulian,^1,3,4 Yu-Wen Chang,^1,3,4 Peng Zhao,^1,3,4 Avis B. Hains,² Stephen G. Waxman,^1,3,4 and Bryan C. Hains^1,3,4

Departments of ¹Neurology and ²Neurobiology and ³Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut 06510, and ⁴Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut 06516

Correspondence should be addressed to Dr. Stephen G. Waxman, The Center for Neuroscience and Regeneration Research, Department of Neurology, Yale University, 950 Campbell Avenue, Building 34, West Haven, CT 06516. Email: stephen.waxman{at}yale.edu

Localized increases in synaptic strength constitute a synaptic basis for learning and memory in the CNS and may also contribute to the maintenance of neuropathic pain after spinal cord injury (SCI) through the de novo formation or elaboration of postsynaptic dendritic structures. To determine whether SCI-induced dendritic spine remodeling contributes to neuronal hyperexcitability and neuropathic pain, we analyzed spine morphometry, localization, and functional influence in dorsal horn (DH) neurons in adult rats 1 month after sham surgery, contusion SCI, and SCI treated with a selective inhibitor of Rac1 activation, NSC23766. After SCI, DH neurons located in lamina IV–V exhibited increased spine density, redistributed spines, and mature spines compared with control neurons, which was associated with enhancement of EPSCs in computer simulations and hyperexcitable responsiveness to innocuous and noxious peripheral stimuli in unit recordings in vivo. SCI animals also exhibited symptoms of tactile allodynia and thermal hyperalgesia. Inhibition of the small GTP-binding protein Rac1 ameliorated post-SCI changes in spine morphology, attenuated injury-induced hyperexcitability of wide-dynamic range neurons, and progressively increased pain thresholds over a 3 d period. This suggests that Rac1 is an important intracellular signaling molecule involved in a spinal dendritic spine pathology associated with chronic neuropathic pain after SCI. Our report provides robust evidence for a novel conceptual bridge between learning and memory on the one hand, and neuropathic pain on the other.

Key words: spinal cord injury; Rac1; dendritic spine; neuropathic pain; dorsal horn; pain; synaptic plasticity

---

Received July 1, 2008; revised Oct. 3, 2008; accepted Oct. 27, 2008.

Correspondence should be addressed to Dr. Stephen G. Waxman, The Center for Neuroscience and Regeneration Research, Department of Neurology, Yale University, 950 Campbell Avenue, Building 34, West Haven, CT 06516. Email: stephen.waxman{at}yale.edu

This article has been cited by other articles:

				M. Sasaki, C. Radtke, A. M. Tan, P. Zhao, H. Hamada, K. Houkin, O. Honmou, and J. D. Kocsis BDNF-Hypersecreting Human Mesenchymal Stem Cells Promote Functional Recovery, Axonal Sprouting, and Protection of Corticospinal Neurons after Spinal Cord Injury J. Neurosci., November 25, 2009; 29(47): 14932 - 14941. [Abstract] [Full Text] [PDF]

				A. M. Tan, J.-S. Choi, S. G. Waxman, and B. C. Hains Dendritic Spine Remodeling After Spinal Cord Injury Alters Neuronal Signal Processing J Neurophysiol, October 1, 2009; 102(4): 2396 - 2409. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help