Journal
FASEB JOURNAL
Volume 16, Issue 12, Pages 1497-1503Publisher
WILEY
DOI: 10.1096/fj.02-0101com
Keywords
hyperalgesia; inflammation; cytokines; nociceptor
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Interleukin 1beta (IL-1beta) is a proinflammatory cytokine that maintains thermal hyperalgesia and facilitates the release of calcitonin gene-related peptide from rat cutaneous nociceptors in vivo and in vitro. Brief applications of IL-1beta to nociceptive neurons yielded a potentiation of heat-activated inward currents (meat) and a shift of activation threshold toward lower temperature without altering intracellular calcium levels. The IL-1 beta-induced heat sensitization was not dependent on G-protein-coupled receptors but was mediated by activation of protein kinases. The nonspecific protein kinase inhibitor staurosporine, the specific protein kinase C inhibitor bisindolyhnaleimide BIM1, and the protein tyrosine kinase inhibitor genistein reduced the sensitizing effect of IL-1beta whereas negative controls were ineffective. RT-PCR and in situ hybridization revealed IL-1RI but not RII expression in neurons rather than surrounding satellite cells in rat dorsal root ganglia. IL-1beta acts on sensory neurons to increase their susceptibility for noxious heat via an IL-1RI/PTK/ PKC-dependent mechanism.
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