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Calpain-mediated down-regulation of myelin-associated glycoprotein in lysophosphatidic acid-induced neuropathic pain

Academic Article
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Overview

authors

  • Xie, W. J.
  • Uchida, H.
  • Nagai, J.
  • Ueda, M.
  • Chun, Jerold
  • Ueda, H.

publication date

  • May 2010

journal

  • Journal of Neurochemistry  Journal

abstract

  • Lysophosphatidic acid receptor (LPA(1)) signaling initiates neuropathic pain through demyelination of the dorsal root (DR). Although LPA is found to cause down-regulation of myelin proteins underlying demyelination, the detailed mechanism remains to be determined. In the present study, we found that a single intrathecal injection of LPA evoked a dose- and time-dependent down-regulation of myelin-associated glycoprotein (MAG) in the DR through LPA(1) receptor. A similar event was also observed in ex vivo DR cultures. Interestingly, LPA-induced down-regulation of MAG was significantly inhibited by calpain inhibitors (calpain inhibitor X, E-64 and E-64d) and LPA markedly induced calpain activation in the DR. The pre-treatment with calpain inhibitors attenuated LPA-induced neuropathic pain behaviors such as hyperalgesia and allodynia. Moreover, we found that sciatic nerve injury activates calpain activity in the DR in a LPA(1) receptor-dependent manner. The E-64d treatments significantly blocked nerve injury-induced MAG down-regulation and neuropathic pain. However, there was no significant calpain activation in the DR by complete Freund's adjuvant treatment, and E-64d failed to show anti-hyperalgesic effects in this inflammation model. The present study provides strong evidence that LPA-induced calpain activation plays a crucial role in the manifestation of neuropathic pain through MAG down-regulation in the DR.

subject areas

  • Animals
  • Calpain
  • Cysteine Proteinase Inhibitors
  • Demyelinating Diseases
  • Disease Models, Animal
  • Enzyme Activation
  • Leucine
  • Lysophospholipids
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myelin-Associated Glycoprotein
  • Neurotoxins
  • Peripheral Nervous System Diseases
  • Receptors, Lysophosphatidic Acid
  • Sciatic Neuropathy
  • Sensory Receptor Cells
  • Spinal Nerve Roots
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Research

keywords

  • calpain
  • demyelination
  • dorsal root
  • lysophosphatidic acid
  • myelin-associated glycoprotein
  • neuropathic pain
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Identity

PubMed Central ID

  • PMC2908211

International Standard Serial Number (ISSN)

  • 0022-3042

Digital Object Identifier (DOI)

  • 10.1111/j.1471-4159.2010.06664.x

PubMed ID

  • 20420580
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Additional Document Info

start page

  • 1002

end page

  • 1011

volume

  • 113

issue

  • 4

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