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MAP kinase and pain.

Publication ,  Journal Article
Ji, R-R; Gereau, RW; Malcangio, M; Strichartz, GR
Published in: Brain Res Rev
April 2009

Mitogen-activated protein kinases (MAPKs) are important for intracellular signal transduction and play critical roles in regulating neural plasticity and inflammatory responses. The MAPK family consists of three major members: extracellular signal-regulated kinases (ERK), p38, and c-Jun N-terminal kinase (JNK), which represent three separate signaling pathways. Accumulating evidence shows that all three MAPK pathways contribute to pain sensitization after tissue and nerve injury via distinct molecular and cellular mechanisms. Activation (phosphorylation) of MAPKs under different persistent pain conditions results in the induction and maintenance of pain hypersensitivity via non-transcriptional and transcriptional regulation. In particular, ERK activation in spinal cord dorsal horn neurons by nociceptive activity, via multiple neurotransmitter receptors, and using different second messenger pathways plays a critical role in central sensitization by regulating the activity of glutamate receptors and potassium channels and inducing gene transcription. ERK activation in amygdala neurons is also required for inflammatory pain sensitization. After nerve injury, ERK, p38, and JNK are differentially activated in spinal glial cells (microglia vs astrocytes), leading to the synthesis of proinflammatory/pronociceptive mediators, thereby enhancing and prolonging pain. Inhibition of all three MAPK pathways has been shown to attenuate inflammatory and neuropathic pain in different animal models. Development of specific inhibitors for MAPK pathways to target neurons and glial cells may lead to new therapies for pain management. Although it is well documented that MAPK pathways can increase pain sensitivity via peripheral mechanisms, this review will focus on central mechanisms of MAPKs, especially ERK.

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Published In

Brain Res Rev

DOI

ISSN

0165-0173

Publication Date

April 2009

Volume

60

Issue

1

Start / End Page

135 / 148

Location

Netherlands

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Sensory Receptor Cells
  • Pain
  • Nociceptors
  • Neurology & Neurosurgery
  • MAP Kinase Signaling System
  • JNK Mitogen-Activated Protein Kinases
  • Inflammation Mediators
  • Humans
  • Extracellular Signal-Regulated MAP Kinases
 

Citation

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Ji, R.-R., Gereau, R. W., Malcangio, M., & Strichartz, G. R. (2009). MAP kinase and pain. Brain Res Rev, 60(1), 135–148. https://doi.org/10.1016/j.brainresrev.2008.12.011
Ji, Ru-Rong, Robert W. Gereau, Marzia Malcangio, and Gary R. Strichartz. “MAP kinase and pain.Brain Res Rev 60, no. 1 (April 2009): 135–48. https://doi.org/10.1016/j.brainresrev.2008.12.011.
Ji R-R, Gereau RW, Malcangio M, Strichartz GR. MAP kinase and pain. Brain Res Rev. 2009 Apr;60(1):135–48.
Ji, Ru-Rong, et al. “MAP kinase and pain.Brain Res Rev, vol. 60, no. 1, Apr. 2009, pp. 135–48. Pubmed, doi:10.1016/j.brainresrev.2008.12.011.
Ji R-R, Gereau RW, Malcangio M, Strichartz GR. MAP kinase and pain. Brain Res Rev. 2009 Apr;60(1):135–148.
Journal cover image

Published In

Brain Res Rev

DOI

ISSN

0165-0173

Publication Date

April 2009

Volume

60

Issue

1

Start / End Page

135 / 148

Location

Netherlands

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Sensory Receptor Cells
  • Pain
  • Nociceptors
  • Neurology & Neurosurgery
  • MAP Kinase Signaling System
  • JNK Mitogen-Activated Protein Kinases
  • Inflammation Mediators
  • Humans
  • Extracellular Signal-Regulated MAP Kinases