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 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.
Shin
Jieun
J
Sensory Research Center, National Creative Research Initiatives, Seoul National University, San 56-1, Shinlim, Kwanak-Gu, Seoul 151-742, Korea.
Cho
Hawon
H
Hwang
Sun Wook
SW
Jung
Jooyoung
J
Shin
Chan Young
CY
Lee
Soon-Youl
SY
Kim
So Hee
SH
Lee
Myung Gull
MG
Choi
Young Hae
YH
Kim
Jinwoong
J
Haber
Nicole Alessandri
NA
Reichling
David B
DB
Khasar
Sachia
S
Levine
Jon D
JD
Oh
Uhtaek
U
D000818:Animals; D000831:Animals, Newborn; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism*; D001920:Bradykinin / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D004224:Diterpenes / Q000493:pharmacokinetics; D005727:Ganglia, Spinal / Q000502:physiology* / Q000503:physiopathology; D006801:Humans; D006930:Hyperalgesia / Q000503:physiopathology*; D007249:Inflammation / Q000503:physiopathology; D015289:Leukotrienes / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins / Q000493:pharmacokinetics; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D018002:Receptors, Bradykinin / Q000502:physiology*; D011955:Receptors, Drug / Q000187:drug effects / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014162:Transfection
D004224:Diterpenes; D015289:Leukotrienes; D009498:Neurotoxins; D018002:Receptors, Bradykinin; D011955:Receptors, Drug; C021201:12-HPETE; C024353:resiniferatoxin; D001092:Arachidonate 12-Lipoxygenase; D001920:Bradykinin