Nociceptors Are Interleukin-1β Sensors
| Autor: | Fumimasa Amaya, Alexander M. Binshtok, Clifford J. Woolf, Daniel Vardeh, Tarek A. Samad, Gary J. Brenner, Katharina Zimmermann, Bruce P. Bean, Haibin Wang, Ru-Rong Ji, Lin Shi |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Male
Patch-Clamp Techniques Time Factors Sensory Receptor Cells Pyridines Interleukin-1beta Biophysics Peripherins Bradykinin Action Potentials Inflammation Nerve Tissue Proteins Tetrodotoxin p38 Mitogen-Activated Protein Kinases Article Proinflammatory cytokine Rats Sprague-Dawley chemistry.chemical_compound Intermediate Filament Proteins Ganglia Spinal Physical Stimulation medicine Animals Enzyme Inhibitors Sensitization Cells Cultured Nerve Fibers Unmyelinated Membrane Glycoproteins Dose-Response Relationship Drug General Neuroscience Sodium channel Imidazoles Nociceptors Rats Nociception Nerve growth factor medicine.anatomical_structure chemistry nervous system Nociceptor medicine.symptom Neuroscience Sodium Channel Blockers |
| Popis: | A cardinal feature of inflammation is heightened pain sensitivity at the site of the inflamed tissue. This results from the local release by immune and injured cells of nociceptor sensitizers, including prostaglandin E2, bradykinin, and nerve growth factor, that reduce the threshold and increase the excitability of the peripheral terminals of nociceptors so that they now respond to innocuous stimuli: the phenomenon of peripheral sensitization. We show here that the proinflammatory cytokine interleukin-1β (IL-1β), in addition to producing inflammation and inducing synthesis of several nociceptor sensitizers, also rapidly and directly activates nociceptors to generate action potentials and induce pain hypersensitivity. IL-1β acts in a p38 mitogen-activated protein kinase (p38 MAP kinase)-dependent manner, to increase the excitability of nociceptors by relieving resting slow inactivation of tetrodotoxin-resistant voltage-gated sodium channels and also enhances persistent TTX-resistant current near threshold. By acting as an IL-1β sensor, nociceptors can directly signal the presence of ongoing tissue inflammation. |
| Databáze: | OpenAIRE |
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