title: Sensitization of TRPV1 by protein kinase C in rats with mono-iodoacetate-induced joint pain.
abstract: To assess the functional changes of Transient receptor potential vanilloid 1 (TRPV1) receptor and to clarify its mechanism in a rat mono-iodoacetate (MIA)-induced joint pain model (MIA rats), which has joint degeneration with cartilage loss similar to osteoarthritis.
  
  
  
  Sensitization of TRPV1 in MIA rats was assessed by transient spontaneous pain behavior induced by capsaicin injection in knee joints and electrophysiological changes of dorsal root ganglion (DRG) neurons innervating knee joints in response to capsaicin. Mechanisms of TRPV1 sensitization were analyzed by a newly developed sandwich enzyme-linked immunosorbent assay that detects phosphorylated TRPV1, followed by functional and expression analyses of protein kinase C (PKC) in vivo and in vitro, which involves TRPV1 phosphorylation.
  
  
  
  Pain-related behavior induced by intra-articular injection of capsaicin was significantly increased in MIA rats compared with sham rats. In addition, capsaicin sensitivity, evaluated by capsaicin-induced inward currents, was significantly increased in DRG neurons of MIA rats. Protein levels of TRPV1 remained unchanged, but phosphorylated TRPV1 at Ser800 increased in DRG neurons of MIA rats. Phosphorylated-PKCɛ (p-PKCɛ) increased and co-localized with TRPV1 in DRG neurons of MIA rats. Capsaicin-induced pain-related behavior in MIA rats was inhibited by intra-articular pretreatment of the PKC inhibitor bisindolylmaleimide I. In addition, intra-articular injection of the PKC activator phorbol 12-myristate 13-acetate increased capsaicin-induced pain-related behavior in normal rats.
  
  
  
  TRPV1 was sensitized at the knee joint and at DRG neurons of MIA rats through PKC activation. Thus, TRPV1 sensitization might be involved in chronic pain caused by osteoarthritis.
authors.affiliation: Pain & Neuroscience, Discovery Research Laboratories for Core Therapeutic Areas, Shionogi & Co., Ltd., 1-1 Futaba-cho, 3-chome, Toyonaka, Osaka 561-0825, Japan. Electronic address: ken.koda@shionogi.co.jp.
authors.forename: K
authors.initials: K
authors.lastname: Koda
authors.affiliation: Pain & Neuroscience, Discovery Research Laboratories for Core Therapeutic Areas, Shionogi & Co., Ltd., 1-1 Futaba-cho, 3-chome, Toyonaka, Osaka 561-0825, Japan. Electronic address: kana.hyakkoku@shionogi.co.jp.
authors.forename: K
authors.initials: K
authors.lastname: Hyakkoku
authors.affiliation: Pain & Neuroscience, Discovery Research Laboratories for Core Therapeutic Areas, Shionogi & Co., Ltd., 1-1 Futaba-cho, 3-chome, Toyonaka, Osaka 561-0825, Japan. Electronic address: kouichi.ogawa@shionogi.co.jp.
authors.forename: K
authors.initials: K
authors.lastname: Ogawa
authors.affiliation: Pain & Neuroscience, Discovery Research Laboratories for Core Therapeutic Areas, Shionogi & Co., Ltd., 1-1 Futaba-cho, 3-chome, Toyonaka, Osaka 561-0825, Japan. Electronic address: keiko.takasu@shionogi.co.jp.
authors.forename: K
authors.initials: K
authors.lastname: Takasu
authors.affiliation: Antibody Therapeutics, Discovery Research Laboratory for Innovative Frontier Medicines, Shionogi & Co., Ltd., 1-1 Futaba-cho, 3-chome, Toyonaka, Osaka 561-0825, Japan. Electronic address: sunao.imai@shionogi.co.jp.
authors.forename: S
authors.initials: S
authors.lastname: Imai
authors.affiliation: Pain & Neuroscience, Discovery Research Laboratories for Core Therapeutic Areas, Shionogi & Co., Ltd., 1-1 Futaba-cho, 3-chome, Toyonaka, Osaka 561-0825, Japan. Electronic address: yusuke.sakurai@shionogi.co.jp.
authors.forename: Y
authors.initials: Y
authors.lastname: Sakurai
authors.affiliation: Pain & Neuroscience, Discovery Research Laboratories for Core Therapeutic Areas, Shionogi & Co., Ltd., 1-1 Futaba-cho, 3-chome, Toyonaka, Osaka 561-0825, Japan. Electronic address: masahide.fujita@shionogi.co.jp.
authors.forename: M
authors.initials: M
authors.lastname: Fujita
authors.affiliation: Pain & Neuroscience, Discovery Research Laboratories for Core Therapeutic Areas, Shionogi & Co., Ltd., 1-1 Futaba-cho, 3-chome, Toyonaka, Osaka 561-0825, Japan. Electronic address: hiroko_ono@shionogi.co.jp.
authors.forename: H
authors.initials: H
authors.lastname: Ono
authors.affiliation: Pain & Neuroscience, Discovery Research Laboratories for Core Therapeutic Areas, Shionogi & Co., Ltd., 1-1 Futaba-cho, 3-chome, Toyonaka, Osaka 561-0825, Japan. Electronic address: miyuki.yamamoto@shionogi.co.jp.
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Biomarker, Biotechnology-Based Medicine, Discovery Research Laboratory for Innovative Frontier Medicines, Shionogi & Co., Ltd., 1-1 Futaba-cho, 3-chome, Toyonaka, Osaka 561-0825, Japan. Electronic address: isao.fukuda@shionogi.co.jp.
authors.forename: I
authors.initials: I
authors.lastname: Fukuda
authors.affiliation: Antibody Therapeutics, Discovery Research Laboratory for Innovative Frontier Medicines, Shionogi & Co., Ltd., 1-1 Futaba-cho, 3-chome, Toyonaka, Osaka 561-0825, Japan. Electronic address: shoji.yamane@shionogi.co.jp.
authors.forename: S
authors.initials: S
authors.lastname: Yamane
authors.affiliation: Biomarker, Biotechnology-Based Medicine, Discovery Research Laboratory for Innovative Frontier Medicines, Shionogi & Co., Ltd., 1-1 Futaba-cho, 3-chome, Toyonaka, Osaka 561-0825, Japan. Electronic address: atsushi.morita@shionogi.co.jp.
authors.forename: A
authors.initials: A
authors.lastname: Morita
authors.affiliation: Pain & Neuroscience, Discovery Research Laboratories for Core Therapeutic Areas, Shionogi & Co., Ltd., 1-1 Futaba-cho, 3-chome, Toyonaka, Osaka 561-0825, Japan. Electronic address: toshiyuki.asaki@shionogi.co.jp.
authors.forename: T
authors.initials: T
authors.lastname: Asaki
authors.affiliation: Pain & Neuroscience, Discovery Research Laboratories for Core Therapeutic Areas, Shionogi & Co., Ltd., 1-1 Futaba-cho, 3-chome, Toyonaka, Osaka 561-0825, Japan. Electronic address: toshiyuki.kanemasa@shionogi.co.jp.
authors.forename: T
authors.initials: T
authors.lastname: Kanemasa
authors.affiliation: Pain & Neuroscience, Discovery Research Laboratories for Core Therapeutic Areas, Shionogi & Co., Ltd., 1-1 Futaba-cho, 3-chome, Toyonaka, Osaka 561-0825, Japan. Electronic address: gaku.sakaguchi@shionogi.co.jp.
authors.forename: G
authors.initials: G
authors.lastname: Sakaguchi
authors.affiliation: Pain & Neuroscience, Discovery Research Laboratories for Core Therapeutic Areas, Shionogi & Co., Ltd., 1-1 Futaba-cho, 3-chome, Toyonaka, Osaka 561-0825, Japan. Electronic address: yasuhide.morioka@shionogi.co.jp.
authors.forename: Y
authors.initials: Y
authors.lastname: Morioka
mesh_terms: D000818:Animals; D018771:Arthralgia; D005727:Ganglia, Spinal; D007461:Iodoacetates; D011493:Protein Kinase C; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007461:Iodoacetates; D011493:Protein Kinase C
keywords: Dorsal root ganglion; Joint pain; Mono-iodoacetate; Protein kinase C; TRPV1