title: Bradykinin-12-lipoxygenase-VR1 signaling pathway for inflammatory hyperalgesia.
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.
authors.affiliation: Sensory Research Center, National Creative Research Initiatives, Seoul National University, San 56-1, Shinlim, Kwanak-Gu, Seoul 151-742, Korea.
authors.forename: Jieun
authors.initials: J
authors.lastname: Shin
authors.forename: Hawon
authors.initials: H
authors.lastname: Cho
authors.forename: Sun Wook
authors.initials: SW
authors.lastname: Hwang
authors.forename: Jooyoung
authors.initials: J
authors.lastname: Jung
authors.forename: Chan Young
authors.initials: CY
authors.lastname: Shin
authors.forename: Soon-Youl
authors.initials: SY
authors.lastname: Lee
authors.forename: So Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Myung Gull
authors.initials: MG
authors.lastname: Lee
authors.forename: Young Hae
authors.initials: YH
authors.lastname: Choi
authors.forename: Jinwoong
authors.initials: J
authors.lastname: Kim
authors.forename: Nicole Alessandri
authors.initials: NA
authors.lastname: Haber
authors.forename: David B
authors.initials: DB
authors.lastname: Reichling
authors.forename: Sachia
authors.initials: S
authors.lastname: Khasar
authors.forename: Jon D
authors.initials: JD
authors.lastname: Levine
authors.forename: Uhtaek
authors.initials: U
authors.lastname: Oh
mesh_terms: 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
chemical_list: D004224:Diterpenes; D015289:Leukotrienes; D009498:Neurotoxins; D018002:Receptors, Bradykinin; D011955:Receptors, Drug; C021201:12-HPETE; C024353:resiniferatoxin; D001092:Arachidonate 12-Lipoxygenase; D001920:Bradykinin