Propargylglycine decreases neuro-immune interaction inducing pain response in temporomandibular joint inflammation model

Autor(es)

Garattini, Emanuela G. ^[1] ; Santos, Bruna M. ^[2] ; Ferrari, Daniele P. ^[1] ; Capel, Camila P. ^[1] ; Francescato, Heloisa D. C. ^[2] ; Coimbra, Terezila M. ^[2] ; Leite-Panissi, Christie R. A. ^[3] ; Branco, Luiz G. S. ^{[2, 1]} ; Nascimento, Glauce C. ^{[2, 1]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dent Sch Ribeirao Preto, Dept Basic & Oral Biol, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Physiol, Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Sch Philosophy Sci & Literature Ribeirao Preto, Psychobiol Grad Program, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: NITRIC OXIDE-BIOLOGY AND CHEMISTRY; v. 93, p. 90-101, DEC 1 2019.
• Citações Web of Science: 0

Resumo

The mechanisms underlying temporomandibular disorders following orofacial pain remain unclear. Hydrogen sulfide (H2S), a newly identified gasotransmitter, has been reported to modulate inflammation. Cystathionine gamma-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-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta) 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-alpha, and IL-1 beta 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. (AU)

• Processo FAPESP: 15/03053-3 - Avaliação de músculo pterigóideo medial e estruturas encefálicas relacionadas à nocicepção orofacial e comportamento emocional em modelo animal de estresse crônico e hipofunção mastigatória
• Beneficiário: Glauce Crivelaro Do Nascimento
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/03645-3 - Papel do sulfeto de hidrogênio na modulação de alodinia orofacial em modelo experimental de hipertensão arterial
• Beneficiário: Camila Porto Capel
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 16/09364-3 - Papel do sulfeto de hidrogênio endógeno na área preóptica modulando a tolerância ao LPS.
• Beneficiário: Bruna Maitan Santos
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 16/17681-9 - Alterações fisiopatológicas durante a inflamação sistêmica
• Beneficiário: Luiz Guilherme de Siqueira Branco
• Modalidade de apoio: Auxílio à Pesquisa - Temático