Role of hydrogen sulfide (H2S) in the inflammatory and nociceptive responses induced by carrageenan in the rat temporomandibular joint

Abstract

Over the last decade, the endogenous production of hydrogen sulfide (H2S), a well known environmental pollutant, has been characterized in mammals, as well as its participation in several organic functions, such as vascular reactivity, mitochondrial activity and inflammatory response. Regarding the latter aspect, and despite some divergences that appear in the literature concerning the pro-or anti-inflammatory effects of H2S, more recent studies demonstrate that the addition of a chemical moiety capable of releasing H2S to the structure of traditional NSAIDs results in compounds that present with lower gastric toxicity and adverse cardiovascular effects in relation to the original non-steroidal anti-inflammatory drugs (NSAIDs), without any loss of their anti-inflammatory action.Our group has demonstrated that treatment of rats with the Lawesson's reagent (an H2S-releasing agent) results in significant reduction of both joint swelling and hyperalgesia secondary to the knee joint arthritis / synovitis induced by the intra-articular injection of carrageenan (CGN). Similarly, other researchers have shown the beneficial effects of H2S donors in other models of knee joint arthritis, such as those induced by kaolin / CGN or Freund's adjuvant. More recently, we demonstrated that the presence of a H2S-releasing moiety in the naproxen molecule, which results in the compound ATB-346, not only does not interfere with the anti-inflammatory activity of the NSAID naproxen in the carrageenan-induced knee joint synovitis in rats, but also avoids the unwanted gastric effects of the latter. However, there are no reports in the literature on the effects of the administration of H2S donors in the temporomandibular joint (TMJ) arthritis.Temporomandibular disorders (TMDs) are a group of diseases associated with the TMJ, masticatory muscles and/or other facial structures. Approximately 50% of the population exhibits some sign of TMDs, and around 10 to 20% of these patients present with severe symptoms, and the consequent drop in quality of life. TMJ arthritis is probably the most important of the TMDs, and the symptoms are partially controlled by the use of NSAIDs and/or low dose glucocorticoids.Given the need for therapeutic alternatives to control these diseases (considering the limitations imposed by the adverse side effects of NSAIDs and corticosteroids), this study aims to assess the effect of H2S donors in a rat model of CGN-induced TMJ arthritis/synovitis, the participation of endogenous H2S in the etiology of the disease and the mechanisms involved. (AU)