Activation of microglia and p38 mitogen-activated protein kinase in the dorsal column nucleus contributes to tactile allodynia following peripheral nerve injury

R. Terayama, S. Omura, N. Fujisawa, T. Yamaai, H. Ichikawa, T. Sugimoto

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

The activation of glial cells in the CNS has been suggested to be involved in abnormal pain sensation after peripheral nerve injury. Previous studies demonstrated phosphorylation of p38 mitogen-activated protein kinase (MAPK) in spinal cord glial cells after peripheral nerve injury, and such phosphorylation has been suggested to be involved in the development of neuropathic pain. The aim of this study was to examine the dorsal column nuclei for phosphorylation of p38 MAPK following peripheral nerve injury and to explore a possibility of its contribution to neuropathic pain. Immunohistochemical labeling for phosphorylated p38 (p-p38) MAPK was performed in histological sections of the rat spinal cord and medulla oblongata after the fifth lumbar (L5) spinal nerve ligation (SNL). The number of p-p38 MAPK-immunoreactive (IR) cells was significantly increased in the L5 dorsal horn and the gracile nucleus ipsilateral to the injury at days 3-21 after SNL. Double immunofluorescence labeling with cell-specific markers revealed that p-p38 MAPK-IR cells co-expressed OX-42, suggesting their microglial identity. Increased immunofluorescence labeling for OX-42 indicated that microglial cells were activated by SNL in the L5 dorsal horn and the gracile nucleus ipsilateral to the injury. Continuous infusion of a p38 MAPK inhibitor into the cisterna magna for 14 days beginning on the day of SNL suppressed the development of tactile allodynia, but not thermal hyperalgesia induced by nerve injury. These results demonstrate that SNL activates p38 MAPK pathway in microglia in the gracile nucleus as well as in the spinal cord dorsal horn. Activation of p38 MAPK in medullary microglia may contribute to the pathogenesis of neuropathic pain.

Original languageEnglish
Pages (from-to)1245-1255
Number of pages11
JournalNeuroscience
Volume153
Issue number4
DOIs
Publication statusPublished - Jun 2 2008

Fingerprint

Peripheral Nerve Injuries
Hyperalgesia
Microglia
p38 Mitogen-Activated Protein Kinases
Spinal Nerves
Ligation
Neuralgia
Phosphorylation
Neuroglia
Fluorescent Antibody Technique
Spinal Cord
Wounds and Injuries
Cisterna Magna
Medulla Oblongata
Protein Kinase Inhibitors
Pain

Keywords

  • behavior
  • gracile nucleus
  • immunohistochemistry
  • neuropathic pain
  • spinal cord
  • spinal nerve ligation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Activation of microglia and p38 mitogen-activated protein kinase in the dorsal column nucleus contributes to tactile allodynia following peripheral nerve injury. / Terayama, R.; Omura, S.; Fujisawa, N.; Yamaai, T.; Ichikawa, H.; Sugimoto, T.

In: Neuroscience, Vol. 153, No. 4, 02.06.2008, p. 1245-1255.

Research output: Contribution to journalArticle

Terayama, R. ; Omura, S. ; Fujisawa, N. ; Yamaai, T. ; Ichikawa, H. ; Sugimoto, T. / Activation of microglia and p38 mitogen-activated protein kinase in the dorsal column nucleus contributes to tactile allodynia following peripheral nerve injury. In: Neuroscience. 2008 ; Vol. 153, No. 4. pp. 1245-1255.
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