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

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 C57b1/6 mice by intraarticular 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.