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

Author(s)

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]}

Affiliation

^[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

• Document type: Journal article
• Source: NITRIC OXIDE-BIOLOGY AND CHEMISTRY; v. 93, p. 90-101, DEC 1 2019.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 15/03053-3 - Evaluation of medial pterygoid muscle and brain structures related to orofacial nociception and emotional behavior in an animal model of chronic stress and masticatory hypofunction
• Grantee: Glauce Crivelaro Do Nascimento
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/03645-3 - Role of hydrogen sulfide in orofacial allodynia modulation in an experimental model of arterial hypertension
• Grantee: Camila Porto Capel
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 16/09364-3 - Role of endogenous preoptic hydrogen sulfide modulating LPS tolerance.
• Grantee: Bruna Maitan Santos
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 16/17681-9 - Pathophysiological changes during systemic inflammation
• Grantee: Luiz Guilherme de Siqueira Branco
• Support Opportunities: Research Projects - Thematic Grants