p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia

Neuron. 2002 Sep 26;36(1):57-68. doi: 10.1016/s0896-6273(02)00908-x.


Peripheral inflammation induces p38 MAPK activation in the soma of C fiber nociceptors in the dorsal root ganglion (DRG) after 24 hr. Inflammation also increases protein, but not mRNA levels, of the heat-gated ion channel TRPV1 (VR1) in these cells, which is then transported to peripheral but not central C fiber terminals. Inhibiting p38 activation in the DRG reduces the increase in TRPV1 in the DRG and inflamed skin and diminishes inflammation-induced heat hypersensitivity without affecting inflammatory swelling or basal pain sensitivity. p38 activation in the DRG is secondary to peripheral production of NGF during inflammation and is required for NGF-induced increases in TRPV1. The activation of p38 in the DRG following retrograde NGF transport, by increasing TRPV1 levels in nociceptor peripheral terminals in a transcription-independent fashion, contributes to the maintenance of inflammatory heat hypersensitivity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / enzymology
  • Hyperalgesia / enzymology*
  • Hyperalgesia / physiopathology
  • Immunohistochemistry
  • Inflammation / enzymology
  • Inflammation / physiopathology
  • Male
  • Mice
  • Mice, Knockout
  • Mitogen-Activated Protein Kinases / metabolism*
  • Nerve Fibers, Unmyelinated / drug effects
  • Nerve Fibers, Unmyelinated / enzymology
  • Nerve Growth Factor / antagonists & inhibitors
  • Nerve Growth Factor / metabolism*
  • Neuralgia / enzymology
  • Neuralgia / physiopathology
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / enzymology*
  • Nociceptors / drug effects
  • Nociceptors / enzymology
  • Posterior Horn Cells / enzymology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Drug / deficiency*
  • Receptors, Drug / drug effects
  • Receptors, Drug / genetics
  • Up-Regulation / drug effects
  • Up-Regulation / physiology*
  • p38 Mitogen-Activated Protein Kinases


  • Receptors, Drug
  • Nerve Growth Factor
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases