Santos Bruna M, Garattini Emanuela G, Branco Luiz G S, Leite-Panissi Christie R A, Nascimento Glauce C
Department of Physiology, Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Department of Morphology, Physiology and Basic Pathology, Ribeirão Preto Dentistry Faculty, University of São Paulo, Ribeirão Preto, SP, Brazil.
Physiol Behav. 2018 May 1;188:128-133. doi: 10.1016/j.physbeh.2018.02.007. Epub 2018 Feb 6.
Hydrogen sulfide (HS) is an endogenous neuromodulator produced mainly by the enzyme cystathionine gamma-lyase (CSE) in peripheral tissues. A pronociceptive role of endogenously produced HS has been previously reported by our group in a model of orofacial inflammatory pain. Using the established persistent orofacial pain rat model induced by complete Freund's adjuvant (CFA) injection into temporomandibular joint (TMJ), we have now investigated the putative role of endogenous HS modulating hypernociceptive responses. Additionally, plasmatic extravasation on TMJ was measured following different treatments by Evans blue dye quantification. Thus, rats were submitted to Von Frey and Formalin tests in orofacial region before and after pharmacological inhibition of the CSE-HS system combined or not with CFA-induced TMJ inflammation. Pretreatment with CSE inhibitor, propargylglycine (PAG; 88.4 μmol/kg) reduced temporomandibular inflammatory pain when injected locally as well as systemically. In particular, local PAG injection seems to be more effective for hypernociceptive responses in orofacial persistent inflammation since its action is evidenced in the majority analyzed periods of the inflammatory process compared to its systemic use. Moreover, local injection seems to act on temporomandibular vascular permeability, evidenced by decreased plasmatic extravasation induced by local PAG administration. Our data are consistent with the notion that the endogenous synthetized gas HS modulates persistent orofacial pain responses revealing the pharmacological importance of the CSE inhibitor as a possible therapeutic target for their control.
硫化氢（HS）是一种内源性神经调节剂，主要由外周组织中的胱硫醚γ-裂解酶（CSE）产生。我们小组先前已在口面部炎性疼痛模型中报道了内源性产生的HS的促痛觉过敏作用。利用通过向颞下颌关节（TMJ）注射完全弗氏佐剂（CFA）建立的持续性口面部疼痛大鼠模型，我们现在研究了内源性HS调节痛觉过敏反应的假定作用。此外，通过伊文思蓝染料定量法在不同处理后测量TMJ处的血浆外渗。因此，在对CSE-HS系统进行药理学抑制联合或不联合CFA诱导的TMJ炎症之前和之后，对大鼠进行口面部区域的von Frey和福尔马林试验。用CSE抑制剂炔丙基甘氨酸（PAG；88.4 μmol/kg）预处理，当局部和全身注射时可减轻颞下颌炎性疼痛。特别是，局部注射PAG似乎对口面部持续性炎症中的痛觉过敏反应更有效，因为与全身使用相比，其作用在炎症过程的大多数分析时间段中都得到了证实。此外，局部注射似乎作用于颞下颌血管通透性，这可通过局部给予PAG诱导的血浆外渗减少来证明。我们的数据与内源性合成气体HS调节持续性口面部疼痛反应的观点一致，这揭示了CSE抑制剂作为其控制的可能治疗靶点的药理学重要性。
