Journal
NEURON
Volume 36, Issue 1, Pages 57-68Publisher
CELL PRESS
DOI: 10.1016/S0896-6273(02)00908-X
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Funding
- NINDS NIH HHS [R 01 NS39518, R01 NS40698, R01 NS040698] Funding Source: Medline
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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.
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