title: Does chloride channel accessory 3 have a role in arthritis pain? A study on murine antigen-induced arthritis.
abstract: Calcium-activated chloride channels (CaCCs) are thought to regulate neuronal excitability, and recently chloride (Cl(-)) regulation in DRG neurons has attracted much attention in pain research. Furthermore, the activity of CaCCs is modified by a family of CLCA proteins. In acute antigen-induced arthritis (AIA), a remarkable up-regulation of the murine chloride channel accessory 3 (mClca3) was shown in dorsal root ganglion (DRG) neurons. Therefore we tested the hypothesis that mClca3 is involved in arthritic pain perception. In mClca3 knock-out mice and wild-type control mice, AIA was induced and measures of inflammation and pain were assessed. In the very acute phase of AIA, joint swelling was reduced in mClca3 knock-out mice. This effect disappeared during the course of AIA. We could not show significant differences in mechanical hyperalgesia between both groups of mice, neither at the acute nor at the chronic stage (21 days of AIA). Additional experiments on thermal hyperalgesia in wild-type and mClca3 knock-out mice in the first 3 days of AIA did not show a difference either. In addition, niflumic acid, an antagonist at CaCCs, did not significantly influence hyperalgesia during AIA. Thus, we were not able to provide evidence for a role of CaCCs, and in particular of mClca3, on the expression of arthritis or inflammation-evoked hyperalgesia.
authors.affiliation: Institute of Physiology I, University Hospital - Friedrich Schiller University Jena, Teichgraben 8, D-07743 Jena, Germany. Electronic address: Matthias.Ebbinghaus@med.uni-jena.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Ebbinghaus
authors.affiliation: Institute of Pathology, University Hospital - Friedrich Schiller University Jena, Ziegelmühlenweg 1, D-07743 Jena, Germany. Electronic address: Mieczyslaw.Gajda@med.uni-jena.de.
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Gajda
authors.affiliation: Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MI 63110, USA. Electronic address: holtzmanm@wustl.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Holtzman
authors.affiliation: Institute of Pharmacology and Toxicology, University Hospital - Friedrich Schiller University Jena, Drackendorfer Str. 1, D-07747 Jena, Germany. Electronic address: Stefan.Schulz@med.uni-jena.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schulz
authors.affiliation: Institute of Physiology I, University Hospital - Friedrich Schiller University Jena, Teichgraben 8, D-07743 Jena, Germany. Electronic address: Hans-Georg.Schaible@med.uni-jena.de.
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Schaible
mesh_terms: D000818:Animals; D001168:Arthritis / Q000378:metabolism* / Q000503:physiopathology; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005620:Freund's Adjuvant; D005727:Ganglia, Spinal / Q000378:metabolism; D006358:Hot Temperature; D006930:Hyperalgesia / Q000503:physiopathology / Q000523:psychology; D018345:Mice, Knockout; D009088:Mucoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009544:Niflumic Acid / Q000494:pharmacology; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology; D058748:Pain Perception
chemical_list: D018118:Chloride Channels; C116464:Clca3a1 protein, mouse; D009088:Mucoproteins; D009544:Niflumic Acid; D005620:Freund's Adjuvant
keywords: AIA; Arthritis; Calcium-activated chloride channels; Chloride channel accessory; Inflammation; Pain; mClca3