Differing effects of exogenous and endogenous hydrogen sulphide in carrageenan-induced knee joint synovitis in the rat
Article first published online: 5 FEB 2010
© 2010 The Authors. Journal compilation © 2010 The British Pharmacological Society
British Journal of Pharmacology
Volume 159, Issue 7, pages 1463–1474, April 2010
How to Cite
Ekundi-Valentim, E., Santos, K., Camargo, E., Denadai-Souza, A., Teixeira, S., Zanoni, C., Grant, A., Wallace, J., Muscará, M. and Costa, S. (2010), Differing effects of exogenous and endogenous hydrogen sulphide in carrageenan-induced knee joint synovitis in the rat. British Journal of Pharmacology, 159: 1463–1474. doi: 10.1111/j.1476-5381.2010.00640.x
- Issue published online: 22 MAR 2010
- Article first published online: 5 FEB 2010
- Received 24 July 2009; revised 5 November 2009; accepted 13 November 2009
- hydrogen sulphide;
- secondary tactile allodynia;
- nitric oxide;
- Lawesson's reagent;
Background and purpose: Recent findings suggest that the noxious gas H2S is produced endogenously, and that physiological concentrations of H2S are able to modulate pain and inflammation in rodents. This study was undertaken to evaluate the ability of endogenous and exogenous H2S to modulate carrageenan-induced synovitis in the rat knee.
Experimental approach: Synovitis was induced in Wistar rats by intra-articular injection of carrageenan into the knee joint. Sixty minutes prior to carrageenan injection, the rats were pretreated with indomethacin, an inhibitor of H2S formation (dl-propargylglycine) or an H2S donor [Lawesson's reagent (LR)].
Key results: Injection of carrageenan evoked knee inflammation, pain as characterized by impaired gait, secondary tactile allodynia of the ipsilateral hindpaw, joint swelling, histological changes, inflammatory cell infiltration, increased synovial myeloperoxidase, protein nitrotyrosine residues, inducible NOS (iNOS) activity and NO production. Pretreatment with LR or indomethacin significantly attenuated the pain responses, and all the inflammatory and biochemical changes, except for the increased iNOS activity, NO production and 3-NT. Propargylglycine pretreatment potentiated synovial iNOS activity (and NO production), and enhanced macrophage infiltration, but had no effect on other inflammatory parameters.
Conclusions and implications: Whereas exogenous H2S delivered to the knee joint can produce a significant anti-inflammatory and anti-nociceptive effect, locally produced H2S exerts little immunomodulatory effect. These data further support the development and use of H2S donors as potential alternatives (or complementary therapies) to the available anti-inflammatory compounds used for treatment of joint inflammation or relief of its symptoms.