Evaluation of the nociceptive response secondary to the individual and combined administration of hydrogen sulfide (H2S) and nitric oxide (no) donors into the rat temporomandibular joint (TMJ)

Abstract

Hydrogen sulfide (H2S) is a gaseous mediator endogenously produced in mammals mainly by the enzymes cystathionine ³-lyase enzyme (CSE) and cystathionine-²-synthase (CBS) using L-cysteine as substrate. A recent work from our laboratory shows that H2S donors, such as the compound GYY-4137 (slow release) or NaHS (spontaneous release), have anti-nociceptive and antiinflammatory effects on the rat temporomandibular joint (TMJ) synovitis induced by the intra-articular injection (i.art.) of carrageenin. In contrast, and despite the controversies about the actual role of nitric oxide (NO) on hyperalgesia, recent results from our laboratory show that the i.art. administration of the NO donor S-nitroso N-acetylpenicillamine - SNAP into the rat TMJ cavity induces mechanical allodinia in a dose-dependent manner. In this way, the objective of this project is to study the interaction between NO and H2S in the rat TMJ in terms of nociception, as well as the possible mechanisms involved. We will first characterize the NO-sGC (soluble guanylate cyclase)-cGMP (cyclic guanosine monophosphate) by both quantification of synovial cGMP concentrations and pharmacological treatment with inhibitors of sGC and/or type V-phosphodiesterase (responsible for cGMP degradation). We will also investigate other NO targets (such as calcium-dependent potassium channels and nitration of protein tyrosine residues), as well as the potential interference with ATP-dependent potassium channels that can be activated by H2S (and sensitive to blockade by glibenclamide). Results will be presented as mean ± standard error of the mean and differences between the groups due to treatments will be assessed by one-way ANOVA followed by Dunnett test, or two-way ANOVA for interactions among treatments and gender/estral cycle. (AU)