Abstract
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
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cells, Cultured
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Dose-Response Relationship, Drug
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Ganglia, Spinal / drug effects
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Ganglia, Spinal / enzymology
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Hyperalgesia / enzymology*
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Hyperalgesia / physiopathology
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Immunohistochemistry
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Inflammation / enzymology
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Inflammation / physiopathology
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Male
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Mice
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Mice, Knockout
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Mitogen-Activated Protein Kinases / metabolism*
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Nerve Fibers, Unmyelinated / drug effects
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Nerve Fibers, Unmyelinated / enzymology
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Nerve Growth Factor / antagonists & inhibitors
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Nerve Growth Factor / metabolism*
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Neuralgia / enzymology
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Neuralgia / physiopathology
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Neurons, Afferent / drug effects
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Neurons, Afferent / enzymology*
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Nociceptors / drug effects
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Nociceptors / enzymology
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Posterior Horn Cells / enzymology
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Rats
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Rats, Sprague-Dawley
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Receptors, Drug / deficiency*
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Receptors, Drug / drug effects
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Receptors, Drug / genetics
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Up-Regulation / drug effects
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Up-Regulation / physiology*
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p38 Mitogen-Activated Protein Kinases
Substances
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Receptors, Drug
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Nerve Growth Factor
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases