Bradykinin-12-Lipoxygenase-VR1 Signaling Pathway for Inflammatory Hyperalgesia

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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2002-07, Vol.99 (15), p.10150-10155
Main Authors: Shin, Jieun, Cho, Hawon, Hwang, Sun Wook, Jung, Jooyoung, Shin, Chan Young, Lee, Soon-Youl, Kim, So Hee, Lee, Myung Gull, Choi, Young Hae, Kim, Jinwoong, Haber, Nicole Alessandri, Reichling, David B., Khasar, Sachia, Levine, Jon D., Oh, Uhtaek
Format: Article
Language:English
Subjects:
Action potentials
Animals
Animals, Newborn
Arachidonate 12-Lipoxygenase - metabolism
Biological Sciences
Bradykinin - pharmacology
Cell Line
Cells, Cultured
Circles
Cytokines
Diterpenes - pharmacokinetics
Fatty acids
Fluorescence
Ganglia, Spinal - physiology
Ganglia, Spinal - physiopathology
Humans
Hyperalgesia
Hyperalgesia - physiopathology
Inflammation - physiopathology
Leukotrienes - metabolism
Nerves
Neurons
Neurons - drug effects
Neurons - physiology
Neurons, Afferent - drug effects
Neurons, Afferent - physiology
Neuroscience
Neurotoxins - pharmacokinetics
Pain
Pain - physiopathology
Rats
Receptors
Receptors, Bradykinin - physiology
Receptors, Drug - drug effects
Receptors, Drug - physiology
Reverse Transcriptase Polymerase Chain Reaction
Sensory neurons
Signal Transduction - drug effects
Signal Transduction - physiology
Transfection
TRPV cation channels
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Description
Summary: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 12-1ipoxygenase 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.152002699