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The Journal of Neuroscience, November 23, 2005, 25(47):10970-10980; doi:10.1523/JNEUROSCI.3066-05.2005

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Development/Plasticity/Repair
Upregulation of the Voltage-Gated Sodium Channel 2 Subunit in Neuropathic Pain Models: Characterization of Expression in Injured and Non-Injured Primary Sensory Neurons

Marie Pertin,^1,2 Ru-Rong Ji,³ Temugin Berta,^1,2 Andrew J. Powell,⁴ Laurie Karchewski,⁶ Simon N. Tate,⁴ Lori L. Isom,⁵ Clifford J. Woolf,⁶ Nicolas Gilliard,¹ Donat R. Spahn,¹ and Isabelle Decosterd^1,2

¹Anesthesiology Pain Research Group, Department of Anesthesiology, Lausanne University Hospital, CH-1011 Lausanne, Switzerland, ²Department of Cell Biology and Morphology, Faculty of Biology and Medicine, Lausanne University, CH-1005 Lausanne, Switzerland, ³Pain Research Center, Department of Anesthesiology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, 02115, ⁴Gene Expression and Protein Biochemistry Department, GlaxoSmithKline Research and Development, Stevenage, Hertfordshire SG1 2NY, United Kingdom, ⁵Department of Pharmacology, The University of Michigan, Ann Arbor, Michigan 48109-0632, and ⁶Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02921

The development of abnormal primary sensory neuron excitability and neuropathic pain symptoms after peripheral nerve injury is associated with altered expression of voltage-gated sodium channels (VGSCs) and a modification of sodium currents. To investigate whether the 2 subunit of VGSCs participates in the generation of neuropathic pain, we used the spared nerve injury (SNI) model in rats to examine 2 subunit expression in selectively injured (tibial and common peroneal nerves) and uninjured (sural nerve) afferents. Three days after SNI, immunohistochemistry and Western blot analysis reveal an increase in the 2 subunit in both the cell body and peripheral axons of injured neurons. The increase persists for >4 weeks, although 2 subunit mRNA measured by real-time reverse transcription-PCR and in situ hybridization remains unchanged. Although injured neurons show the most marked upregulation,2 subunit expression is also increased in neighboring non-injured neurons and a similar pattern of changes appears in the spinal nerve ligation model of neuropathic pain. That increased 2 subunit expression in sensory neurons after nerve injury is functionally significant, as demonstrated by our finding that the development of mechanical allodynia-like behavior in the SNI model is attenuated in 2 subunit null mutant mice. Through its role in regulating the density of mature VGSC complexes in the plasma membrane and modulating channel gating, the 2 subunit may play a key role in the development of ectopic activity in injured and non-injured sensory afferents and, thereby, neuropathic pain.

Key words: pain; neuropathic pain; sodium channel; subunit; nerve injury; animal model

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Received March 23, 2005; revised October 12, 2005; accepted October 12, 2005.

This article has been cited by other articles:

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				A. M. Rush, T. R. Cummins, and S. G. Waxman Multiple sodium channels and their roles in electrogenesis within dorsal root ganglion neurons J. Physiol., February 15, 2007; 579(1): 1 - 14. [Abstract] [Full Text] [PDF]

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