The cytokine TNFalpha increases the proportion of DRG neurones expressing the TRPV1 receptor via the TNFR1 receptor and ERK activation.
TNFalpha is involved in the generation of hyperalgesia in pathological states such as neuropathy and inflammation. The pronociceptive action of TNFalpha may be mediated at least in part by activation of the TRPV1 receptor which transduces heat stimuli in primary nociceptive afferents and mediates thermal hyperalgesia. In the present study, we investigated in cultured dorsal root ganglion (DRG) neurones, the somata of primary afferent fibres, whether TNFalpha increases TRPV1 receptor expression. We found that long-term exposure of DRG neurones of both rat and mouse to TNFalpha significantly increased the proportion of DRG neurones expressing TRPV1 receptor-like immunoreactivity. This TNFalpha effect was abolished in mice DRG neurones when DRG cultures were obtained from tnfr1/2-/- and tnfr1-/-, but not from tnfr2-/- mice. Furthermore, we found that activation of ERK but not of p38 kinase or cyclooxygenases is critically involved in the TNFalpha-induced increase of TRPV1 receptor expression.
Hensellek
Susanne
S
Institute of Physiology I, Friedrich Schiller University of Jena, Teichgraben 8, D-07740 Jena, Germany.
Brell
Patrice
P
Schaible
Hans-Georg
HG
Bräuer
Rolf
R
Segond von Banchet
Gisela
G
D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D006930:Hyperalgesia / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D009619:Nociceptors / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D047888:Receptors, Tumor Necrosis Factor, Type I; D050916:TRPV Cation Channels; C506237:Tnfrsf1a protein, rat; C493922:Trpv1 protein, rat; D014409:Tumor Necrosis Factor-alpha; D048049:Extracellular Signal-Regulated MAP Kinases