p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia.
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.
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000187:drug effects / Q000201:enzymology; D006930:Hyperalgesia / Q000201:enzymology* / Q000503:physiopathology; D007150:Immunohistochemistry; D007249:Inflammation / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000201:enzymology; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009437:Neuralgia / Q000201:enzymology / Q000503:physiopathology; D009475:Neurons, Afferent / Q000187:drug effects / Q000201:enzymology*; D009619:Nociceptors / Q000187:drug effects / Q000201:enzymology; D020671:Posterior Horn Cells / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000172:deficiency* / Q000187:drug effects / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases
D011955:Receptors, Drug; D020932:Nerve Growth Factor; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases