Submitted on June 20, 2008
Revised on July 18, 2008
Accepted on July 26, 2008
Leukocyte Trafficking and Pain Behavioural Responses to a Hydrogen Sulphide Donor in Acute Monoarthritis
Benjamin Andruski, Donna-Marie McCafferty1, Teegan Ignacy, Brandie Millen, and Jason J. McDougall1*
1 University of Calgary
* To whom correspondence should be addressed. E-mail: mcdougaj{at}ucalgary.ca.
Hydrogen sulphide (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 anaesthetized 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 co-administration of the KATP 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 signalling molecule in rodent knee joints. H2S exhibits potent anti-inflammatory properties, but with no observable effect on joint pain.
