Physiol. Genomics Journal of Applied Physiology
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Physiol. Genomics 29: 215-230, 2007. First published January 9, 2007; doi:10.1152/physiolgenomics.00255.2006 Free Article
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Received 6 November 2006; accepted in final form 6 January 2007.
Physiological Genomics 29:215-230 (2007)
1094-8341/07 $8.00 © 2007 American Physiological Society

Proteomics study of neuropathic and nonneuropathic dorsal root ganglia: altered protein regulation following segmental spinal nerve ligation injury

Naoka Komori 1, Nobuaki Takemori 1, Hee Kee Kim 3, Anil Singh 1, Seon-Hee Hwang 3, Robert D. Foreman 2, Kyungsoon Chung 3, Jin Mo Chung 3 and Hiroyuki Matsumoto 1

1 Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
2 Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
3 Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas

Peripheral nerve injury is often followed by the development of severe neuropathic pain. Nerve degeneration accompanied by inflammatory mediators is thought to play a role in generation of neuropathic pain. Neuronal cell death follows axonal degeneration, devastating a vast number of molecules in injured neurons and the neighboring cells. Because we have little understanding of the cellular and molecular mechanisms underlying neuronal cell death triggered by nerve injury, we conducted a proteomics study of rat 4th and 5th lumbar (L4 and L5) dorsal root ganglion (DRG) after L5 spinal nerve ligation. DRG proteins were displayed on two-dimensional gels and analyzed through quantitative densitometry, statistical validation of the quantitative data, and peptide mass fingerprinting for protein identification. Among {approx}1,300 protein spots detected on each gel, we discovered 67 proteins that were tightly regulated by nerve ligation. We find that the injury to primary sensory neurons turned on multiple cellular mechanisms critical for the structural and functional integrity of neurons and for the defense against oxidative damage. Our data indicate that the regulation of metabolic enzymes was carefully orchestrated to meet the altered energy requirement of the DRG cells. Our data also demonstrate that ligation of the L5 spinal nerve led to the upregulation in the L4 DRG of the proteins that are highly expressed in embryonic sensory neurons. To understand the molecular mechanisms underlying neuropathic pain, we need to comprehend such dynamic aspect of protein modulations that follow nerve injury.

circulatory proteins; dorsal root ganglion protein expression profiles; isozyme switching; myogenic proteins; peripheral neuropathy




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