Bradykinin-12-lipoxygenase-VR1 signaling pathway for inflammatory hyperalgesia

Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):10150-5. doi: 10.1073/pnas.152002699. Epub 2002 Jul 3.

Abstract

The capsaicin-sensitive vanilloid receptor (VR1) was recently shown to play an important role in inflammatory pain (hyperalgesia), but the underlying mechanism is unknown. We hypothesized that pain-producing inflammatory mediators activate capsaicin receptors by inducing the production of fatty acid agonists of VR1. This study demonstrates that bradykinin, acting at B2 bradykinin receptors, excites sensory nerve endings by activating capsaicin receptors via production of 12-lipoxygenase metabolites of arachidonic acid. This finding identifies a mechanism that might be targeted in the development of new therapeutic strategies for the treatment of inflammatory pain.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Arachidonate 12-Lipoxygenase / metabolism*
  • Bradykinin / pharmacology*
  • Cell Line
  • Cells, Cultured
  • Diterpenes / pharmacokinetics
  • Ganglia, Spinal / physiology*
  • Ganglia, Spinal / physiopathology
  • Humans
  • Hyperalgesia / physiopathology*
  • Inflammation / physiopathology
  • Leukotrienes / metabolism
  • Neurons / drug effects
  • Neurons / physiology*
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / physiology*
  • Neurotoxins / pharmacokinetics
  • Pain / physiopathology*
  • Rats
  • Receptors, Bradykinin / physiology*
  • Receptors, Drug / drug effects
  • Receptors, Drug / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Transfection

Substances

  • Diterpenes
  • Leukotrienes
  • Neurotoxins
  • Receptors, Bradykinin
  • Receptors, Drug
  • 12-HPETE
  • resiniferatoxin
  • Arachidonate 12-Lipoxygenase
  • Bradykinin