The mechanisms underlying temporomandibular disorders following orofacial pain remain unclear. Hydrogen sulfide (H2S), a newly identified gasotransmitter, has been reported to modulate inflammation. Cystathionine γ-lyase (CSE) is responsible for the systemical production of H2S, which exerts both pro- and antinociceptive effects through inflammation. In the current study, we investigated whether the endogenous H2S production pathway contributes to arousal and maintenance of orofacial inflammatory pain, through the investigation of the effects of a CSE inhibitor, propargyglycine (PAG), in a rat CFA (Complete Freund Adjuvant)-induced temporomandibular inflammation model to mimic persistent pain in the orofacial region. For this, rats received either CFA or saline in the temporomandibular joints (TMJs), and after 3 or 14 days, they received a single injection of PAG or saline and were evaluated for nociception with the von Frey and formalin test. Also, pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were analyzed in TMJs and trigeminal ganglion (TG). In this last one, glial cells reactivity was also verified. Endogenous H2S production rate were measured in both, TMJ and TG. Our results indicated decreased allodynia and hyperalgesic responses in rats submitted to CFA after injection of PAG. Moreover, PAG inhibited leucocyte migration to temporomandibular synovial fluid after 3 and 14 days of inflammation. PAG was able to reduce levels of CBS, CSE, TNF-α, and IL-1β in the TMJ and TG, after 13 days of CFA injection. The observed increased activation of glial cells in the trigeminal ganglia on the 14th day of inflammation can be prevented by the highest dose of PAG. Finally, CBS and CSE expression, and endogenous H2S production rate in the TMJ and TG was found higher in rats with persistent temporomandibular inflammation compared to rats injected with saline and PAG was able to prevent this elevation. Our results elucidated the molecular mechanisms by which H2S exerts its pro-inflammatory and pro-nociceptive role in the orofacial region by alterations in both local tissue and TG.

中文翻译：

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炔丙基甘氨酸减少颞下颌关节炎症模型中的神经免疫相互作用，诱导疼痛反应。

口腔疼痛后颞下颌疾病的潜在机制仍不清楚。据报道，硫化氢（H2S）是一种新发现的气体传输剂，可调节炎症。胱硫醚γ-裂解酶（CSE）负责系统产生H2S，H2S通过炎症发挥促伤害感受和抗伤害感受的作用。在本研究中，我们通过研究大鼠CFA（完全弗氏佐剂）诱导的CSE抑制剂炔丙基甘氨酸（PAG）的作用，研究了内源性H2S产生途径是否有助于唤醒和维持口面炎性疼痛。颞下颌炎症模型模拟口面部持续性疼痛。为此，大鼠在颞下颌关节（TMJ）中接受了CFA或生理盐水，在3或14天后，他们接受了单剂PAG或盐水的注射，并通过von Frey和福尔马林测试评估了伤害感受。此外，在TMJ和三叉神经节（TG）中分析了促炎细胞因子，肿瘤坏死因子-α（TNF-α）和白介素-1β（IL-1β）。在这最后一个中，还证实了神经胶质细胞的反应性。在TMJ和TG中均测量了内源性H2S生产率。我们的结果表明，注射PAG后提交CFA的大鼠的异常性疼痛和痛觉过敏反应减少。此外，PAG抑制发炎3天和14天后白细胞迁移至颞下颌滑液。注射CFA 13天后，PAG能够降低TMJ和TG中CBS，CSE，TNF-α和IL-1β的水平。最高剂量的PAG可以预防炎症的第14天在三叉神经节中神经胶质细胞活化的增加。最后，与注射盐水和PAG能够预防这种升高的大鼠相比，持续性颞下颌炎症的大鼠的CJ和CSE表达以及TMJ和TG中内源性H2S产生率更高。我们的研究结果阐明了H2S通过改变局部组织和TG在口腔区域发挥其促炎和伤害感受作用的分子机制。