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JAK-STAT3 pathway regulates spinal astrocyte proliferation and neuropathic pain maintenance in rats.

Publication ,  Journal Article
Tsuda, M; Kohro, Y; Yano, T; Tsujikawa, T; Kitano, J; Tozaki-Saitoh, H; Koyanagi, S; Ohdo, S; Ji, R-R; Salter, MW; Inoue, K
Published in: Brain
April 2011

Neuropathic pain, a debilitating pain condition, is a common consequence of damage to the nervous system. Optimal treatment of neuropathic pain is a major clinical challenge because the underlying mechanisms remain unclear and currently available treatments are frequently ineffective. Emerging lines of evidence indicate that peripheral nerve injury converts resting spinal cord glia into reactive cells that are required for the development and maintenance of neuropathic pain. However, the mechanisms underlying reactive astrogliosis after nerve injury are largely unknown. In the present study, we investigated cell proliferation, a critical process in reactive astrogliosis, and determined the temporally restricted proliferation of dorsal horn astrocytes in rats with spinal nerve injury, a well-known model of neuropathic pain. We found that nerve injury-induced astrocyte proliferation requires the Janus kinase-signal transducers and activators of transcription 3 signalling pathway. Nerve injury induced a marked signal transducers and activators of transcription 3 nuclear translocation, a primary index of signal transducers and activators of transcription 3 activation, in dorsal horn astrocytes. Intrathecally administering inhibitors of Janus kinase-signal transducers and activators of transcription 3 signalling to rats with nerve injury reduced the number of proliferating dorsal horn astrocytes and produced a recovery from established tactile allodynia, a cardinal symptom of neuropathic pain that is characterized by pain hypersensitivity evoked by innocuous stimuli. Moreover, recovery from tactile allodynia was also produced by direct suppression of dividing astrocytes by intrathecal administration of the cell cycle inhibitor flavopiridol to nerve-injured rats. Together, these results imply that the Janus kinase-signal transducers and activators of transcription 3 signalling pathway are critical transducers of astrocyte proliferation and maintenance of tactile allodynia and may be a therapeutic target for neuropathic pain.

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Published In

Brain

DOI

EISSN

1460-2156

Publication Date

April 2011

Volume

134

Issue

Pt 4

Start / End Page

1127 / 1139

Location

England

Related Subject Headings

  • Statistics, Nonparametric
  • Spinal Nerves
  • Signal Transduction
  • STAT3 Transcription Factor
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rats, Wistar
  • Rats
  • Neurology & Neurosurgery
  • Neuralgia
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
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Tsuda, M., Kohro, Y., Yano, T., Tsujikawa, T., Kitano, J., Tozaki-Saitoh, H., … Inoue, K. (2011). JAK-STAT3 pathway regulates spinal astrocyte proliferation and neuropathic pain maintenance in rats. Brain, 134(Pt 4), 1127–1139. https://doi.org/10.1093/brain/awr025
Tsuda, Makoto, Yuta Kohro, Takayuki Yano, Tomoko Tsujikawa, Junko Kitano, Hidetoshi Tozaki-Saitoh, Satoru Koyanagi, et al. “JAK-STAT3 pathway regulates spinal astrocyte proliferation and neuropathic pain maintenance in rats.Brain 134, no. Pt 4 (April 2011): 1127–39. https://doi.org/10.1093/brain/awr025.
Tsuda M, Kohro Y, Yano T, Tsujikawa T, Kitano J, Tozaki-Saitoh H, et al. JAK-STAT3 pathway regulates spinal astrocyte proliferation and neuropathic pain maintenance in rats. Brain. 2011 Apr;134(Pt 4):1127–39.
Tsuda, Makoto, et al. “JAK-STAT3 pathway regulates spinal astrocyte proliferation and neuropathic pain maintenance in rats.Brain, vol. 134, no. Pt 4, Apr. 2011, pp. 1127–39. Pubmed, doi:10.1093/brain/awr025.
Tsuda M, Kohro Y, Yano T, Tsujikawa T, Kitano J, Tozaki-Saitoh H, Koyanagi S, Ohdo S, Ji R-R, Salter MW, Inoue K. JAK-STAT3 pathway regulates spinal astrocyte proliferation and neuropathic pain maintenance in rats. Brain. 2011 Apr;134(Pt 4):1127–1139.
Journal cover image

Published In

Brain

DOI

EISSN

1460-2156

Publication Date

April 2011

Volume

134

Issue

Pt 4

Start / End Page

1127 / 1139

Location

England

Related Subject Headings

  • Statistics, Nonparametric
  • Spinal Nerves
  • Signal Transduction
  • STAT3 Transcription Factor
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rats, Wistar
  • Rats
  • Neurology & Neurosurgery
  • Neuralgia
  • Male