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.
Ji, R-R; Samad, TA; Jin, S-X; Schmoll, R; Woolf, CJ
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