title: Reactive oxygen species derived from NOX1/NADPH oxidase enhance inflammatory pain.
abstract: The involvement of reactive oxygen species (ROS) in an augmented sensitivity to painful stimuli (hyperalgesia) during inflammation has been suggested, yet how and where ROS affect the pain signaling remain unknown. Here we report a novel role for the superoxide-generating NADPH oxidase in the development of hyperalgesia. In mice lacking Nox1 (Nox1(-/Y)), a catalytic subunit of NADPH oxidase, thermal and mechanical hyperalgesia was significantly attenuated, whereas no change in nociceptive responses to heat or mechanical stimuli was observed. In dorsal root ganglia (DRG) neurons of Nox1(+/Y), pretreatment with chemical mediators bradykinin, serotonin, or phorbol 12-myristate 13-acetate (PMA) augmented the capsaicin-induced calcium increase, whereas this increase was significantly attenuated in DRG neurons of Nox1(-/Y). Concomitantly, PMA-induced translocation of PKCepsilon was markedly perturbed in Nox1(-/Y) or Nox1(+/Y) DRG neurons treated with ROS-scavenging agents. In cells transfected with tagged PKCepsilon, hydrogen peroxide induced translocation and a reduction in free sulfhydryls of full-length PKCepsilon but not of the deletion mutant lacking the C1A domain. These findings indicate that NOX1/NADPH oxidase accelerates the translocation of PKCepsilon in DRG neurons, thereby enhancing the TRPV1 activity and the sensitivity to painful stimuli.
authors.affiliation: Department of Pharmacology and Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ibi
authors.forename: Kuniharu
authors.initials: K
authors.lastname: Matsuno
authors.forename: Dai
authors.initials: D
authors.lastname: Shiba
authors.forename: Masato
authors.initials: M
authors.lastname: Katsuyama
authors.forename: Kazumi
authors.initials: K
authors.lastname: Iwata
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kakehi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Kazunori
authors.initials: K
authors.lastname: Sango
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Shirai
authors.forename: Takahiko
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Shuji
authors.initials: S
authors.lastname: Kaneko
authors.forename: Naoaki
authors.initials: N
authors.lastname: Saito
authors.forename: Chihiro
authors.initials: C
authors.lastname: Yabe-Nishimura
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016166:Free Radical Scavengers / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D000074624:NADPH Oxidase 1; D009475:Neurons, Afferent / Q000378:metabolism; D009619:Nociceptors / Q000378:metabolism* / Q000503:physiopathology; D018384:Oxidative Stress / Q000502:physiology*; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D051744:Protein Kinase C-epsilon / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000187:drug effects / Q000378:metabolism
chemical_list: D016166:Free Radical Scavengers; D018836:Inflammation Mediators; D017382:Reactive Oxygen Species; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; C000614711:NOX1 protein, mouse; D051744:Protein Kinase C-epsilon
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