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INFLAMMATION, CYTOKINES, NEUROIMMUNE INTERACTIONS

Leukocyte trafficking and pain behavioral responses to a hydrogen sulfide donor in acute monoarthritis

Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada

Submitted 20 June 2008 ; accepted in final form 26 July 2008

Hydrogen sulfide (H₂S) 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 H₂S donor (Na₂S) 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 Na₂S 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 Na₂S on joint pain in control and inflamed rats was determined by hindlimb incapacitance and von Frey hair algesiometry. Local administration of an H₂S 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 Na₂S to inflamed joints caused a pronounced vasoconstrictor response; however, there was no observable effect of Na₂S on joint pain. These findings establish H₂S as a novel signaling molecule in rodent knee joints. H₂S exhibits potent anti-inflammatory properties, but with no detectable effect on joint pain.

arthritis; blood flow; intravital microscopy; potassium channels