title: Leukocyte trafficking and pain behavioral responses to a hydrogen sulfide donor in acute monoarthritis.
abstract: Hydrogen sulfide (H(2)S) is an endogenous gaseous mediator with the ability to modulate tissue inflammation and pain. The aim of this study was to determine the effect of an H(2)S donor (Na(2)S) on leukocyte-endothelium interactions, blood flow, and pain sensation in acutely inflamed knee joints. Acute arthritis was induced in urethane anesthetized C57bl/6 mice by intra-articular injection of kaolin/carrageenan (24-h recovery), and the effect of local administration of Na(2)S on leukocyte trafficking was measured by intravital microscopy. Synovial blood flow was measured in inflamed knees by laser Doppler perfusion imaging. Finally, the effect of an intra-articular injection of Na(2)S on joint pain in control and inflamed rats was determined by hindlimb incapacitance and von Frey hair algesiometry. Local administration of an H(2)S donor to inflamed knees caused a dose-dependent reduction in leukocyte adherence and an increase in leukocyte velocity. These effects could be inhibited by coadministration of the ATP-sensitive K(+) channel blocker glibenclamide. Local administration of Na(2)S to inflamed joints caused a pronounced vasoconstrictor response; however, there was no observable effect of Na(2)S on joint pain. These findings establish H(2)S as a novel signaling molecule in rodent knee joints. H(2)S exhibits potent anti-inflammatory properties, but with no detectable effect on joint pain.
authors.affiliation: Dept. of Physiology and Biophysics, Univ. of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta T2N 4N1, Canada.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Andruski
authors.forename: Donna-Marie
authors.initials: DM
authors.lastname: McCafferty
authors.forename: Teegan
authors.initials: T
authors.lastname: Ignacy
authors.forename: Brandie
authors.initials: B
authors.lastname: Millen
authors.forename: Jason J
authors.initials: JJ
authors.lastname: McDougall
mesh_terms: D000208:Acute Disease; D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology*; D001522:Behavior, Animal / Q000502:physiology; D002351:Carrageenan / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007616:Kaolin / Q000494:pharmacology; D007719:Knee Joint / Q000098:blood supply / Q000276:immunology; D007962:Leukocytes / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology*; D010812:Physical Stimulation; D011434:Proprioception / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013440:Sulfides / Q000494:pharmacology*
chemical_list: D013440:Sulfides; D007616:Kaolin; D002351:Carrageenan; C025451:sodium bisulfide; D006862:Hydrogen Sulfide