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Activation of p38 mitogen-activated protein kinase in spinal microglia is a critical link in inflammation-induced

Camilla I Svensson1, Martin Marsala, Anna Westerlund

  • 1Department of Anesthesiology, University of California, San Diego, La Jolla, California, USA. csvensson@ucsd.edu

Journal of Neurochemistry
|September 3, 2003
PubMed

Insights

p38 mitogen-activated protein kinase (MAPK) inhibitors reduced pain in models of spinal sensitization. Activated spinal microglia, not neurons, play a role in processing inflammation-induced pain signals.

Area of Science:

  • Neuroscience
  • Pain Research
  • Molecular Biology

Background:

  • p38 mitogen-activated protein kinase (MAPK) is implicated in pain signaling.
  • Its role in spinal nociception, particularly in relation to microglia, requires further elucidation.

Purpose of the Study:

  • To investigate the role of spinal p38 MAPK in nociception and spinal sensitization.
  • To determine the cellular localization of activated p38 MAPK in the spinal cord.

Main Methods:

  • Utilized p38 MAPK inhibitors (SB20358, SD-282) in rodent models of nociception.
  • Assessed pain thresholds and hyperalgesia.
  • Employed immunocytochemistry and double-staining to identify cell types expressing phosphorylated p38 MAPK in the spinal cord.

Main Results:

  • Phosphorylated p38 MAPK increased in the spinal cord after noxious stimuli and co-localized with microglia in the dorsal horn.
  • p38 MAPK inhibitors attenuated hyperalgesia in models of spinal sensitization but not acute pain.
  • Inhibitor pretreatment blocked spinal sensitization markers (COX-2, Fos) but post-treatment did not.

Conclusions:

  • Spinal p38 MAPK activation is crucial for inflammation-induced hyperalgesia and spinal sensitization.
  • Activated microglia in the spinal cord are key players in processing pain signals during inflammation.

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