Nociceptors are interleukin-1β sensors

Alexander M. Binshtok, Haibin Wang, Katharina Zimmermann, Fumimasa Amaya, Daniel Vardeh, Lin Shi, Gary J. Brenner, Ru Rong Ji, Bruce P. Bean, Clifford J. Woolf, Tarek A. Samad

Research output: Contribution to journalArticlepeer-review

520 Scopus citations


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.

Original languageAmerican English
Pages (from-to)14062-14073
Number of pages12
JournalJournal of Neuroscience
Issue number52
StatePublished - 24 Dec 2008
Externally publishedYes


  • Dorsal root ganglion
  • Excitability
  • Inflammation
  • Interleukin
  • Nociception
  • Sodium channel


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