P2X7-induced nociception in the temporomandibular joint of rats depends on inflammatory mechanisms and C-fibres sensitization

Autor(es)

Teixeira, Juliana M. ^[1] ; Pimentel, Rafael M. ^[1] ; Abdalla, Henrique B. ^[1] ; de Sousa, Hortencia M. X. ^[2] ; Macedo, Cristina G. ^[1] ; Napimoga, Marcelo H. ^[3] ; Tambeli, Claudia H. ^[4] ; Oliveira-Fusaro, Maria C. G. ^[5] ; Clemente-Napimoga, Juliana T. ^[1]

Afiliação do(s) autor(es)

^[1] Inst Pesquisas Sao Leopoldo Mandic, Fac Sao Leopoldo Mandic, Area Fisiol, Campinas - Brazil

^[2] State Univ Campinas UNICAMP, Piracicaba Dent Sch, Dept Physiol, Lab Orofacial Pain, Piracicaba - Brazil

^[3] Inst Pesquisas Sao Leopoldo Mandic, Fac Sao Leopoldo Mandic, Area Imunol, Campinas - Brazil

^[4] State Univ Campinas UNICAMP, Inst Biol, Dept Struct & Funct Biol, Campinas - Brazil

^[5] State Univ Campinas UNICAMP, Lab Studies Pain & Inflammat, Sch Appl Sci, Limeira, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF PAIN; v. 25, n. 5 FEB 2021.
• Citações Web of Science: 0

Resumo

Background P2X7 receptors are responsible for triggering inflammatory responses contributing to processes of pain in articular tissues. This study aimed to investigate whether the activation of the P2X7 receptor located in the temporomandibular joint (TMJ) tissues induces nociception through an inflammatory mechanisms and/or the activation of C-fibres (small-diameter primary afferents) of rats' TMJ. Methods The TMJ hypernociception induced by the activation of P2X7 receptor was assessed by measuring the behavioural nociceptive responses. After behavioural experiments, the animals were terminally anaesthetized and periarticular tissues were removed and homogenate for enzyme-linked immunosorbent assay, leukocyte infiltration and western blotting analysis. Results The nonselective P2X7 receptor agonist BzATP induced a dose-dependent TMJ nociception, which was blocked by the selective P2X7 receptor antagonist A-438079. The co-administration of the selective beta 2-adrenoceptor antagonist (ICI-118,551) and the pre-treatment with cyclooxygenase inhibitor indomethacin or with the nonspecific selectin inhibitor Fucoidan significantly reduced BzATP-induced TMJ nociception. BzATP also induced an increase of pro-inflammatory cytokines TNF alpha, IL-1 beta and CINC-1 levels, as well as leukocyte recruitment in TMJ tissue, effects that were reduced by A-438079. Moreover BzATP-induced TMJ nociception was inhibited in rats neonatal-treated with Capsaicin (depleting C-fibers). Finally, BzATP-induced an increase in TRPV1 expression in TMJ tissue. Conclusions These findings suggest that P2X7 receptor activation in TMJ of rats induces nociceptive responses mediated by sympathomimetic amines, prostaglandins, leukocyte migration and increased levels of pro-inflammatory cytokines. Furthermore, the P2X7 receptor activation induces nociceptive responses dependent on the activation of the primary afferent nociceptors of rats' TMJ. Significance The activation of P2X7 receptors has an essential role in TMJ nociception and could be an interesting target to control the inflammatory pain in temporomandibular disorders. (AU)

• Processo FAPESP: 05/59179-3 - Envolvimento dos subtipos de receptores P2X na dor inflamatória da ATM
• Beneficiário: Juliana Maia Teixeira
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 17/22334-9 - Uso de sistemas de liberação de fármacos para o desenvolvimento e aplicabilidade de agentes anti-inflamatórios com potencial efeito imunomodulador e neuroprotetor
• Beneficiário: Marcelo Henrique Napimoga
• Modalidade de apoio: Auxílio à Pesquisa - Temático