Modulatory effect of botulinum toxin type A on the microglial P2X7/CatS/FKN activated-pathway in antigen-induced arthritis of the temporomandibular joint of rats

Autor(es)

Manuel Munoz-Lora, Victor Ricardo ^{[1, 2]} ; Abdalla, Henrique Ballassini ^[3] ; Del Bel Cury, Altair Antoninha ^[1] ; Clemente-Napimoga, Juliana Trindade ^[3]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, UNICAMP, Piracicaba Dent Sch, Dept Prosthodont & Periodontol, Piracicaba, SP - Brazil

^[2] Univ Ibirapuera, Sch Dent, Dent Res Div, Sao Paulo, SP - Brazil

^[3] Inst & Ctr Pesquisas Sao Leopoldo Mandic, Fac Sao Leopoldo Mandic, Lab Neuroimmune Interface Pain Res, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Toxicon; v. 187, p. 116-121, NOV 2020.
• Citações Web of Science: 1

Resumo

Analgesic mechanism of Botulinum toxin type A (BoNT/A) involves retrograde axonal transport to central nervous system, where it may interact with sensory neurons. Though, some authors suggested that BoNT/A antinociceptive action may also be associated with the inhibition intracellular factors and neummodulators expressed by immune cells, especially by microglia. Antigen-induced arthritis in the temporomandibular joint (TMJ) of rats is signal by P2X7 receptor/Cathepsin S (CatS)/Fractalkine (FKN) microglia-activated pathway. Thus, we aimed to evaluate the possible modulatory effect of an intra-TMJ injection of BoNT/A on the P2X7/ CatS/FKN microglia-activated pathway in the trigeminal subnucleus caudalis of rats with antigen-induced arthritis of the TMJ. A model of antigen-induced arthritis was used on Wistar rats (n = 40) by systemic injections of an emulsion containing complete Freund's adjuvant and methylated bovine serum albumin (mBSA) diluted in PBS. The arthritic condition was stablished by an intra-TMJ injection of mBSA (10 mu g/TMJ/week) for 3 weeks. Then, animals were treated with an intra-TMJ injection of BoNT/A (onabotulinumtoxinA, Allergan (R); 7U/ kg) or vehicle saline. Animals were euthanized 24 h, 7 or 14 days after BoNT/A treatment and their trigeminal nucleus caudalis was harvested to evaluate the protein level of microglial purinergic P2X7 receptor and CX3 chemokine receptor 1 (CX3CR1) by Western blot, and to measure the protein level of micmglial modulators CatS, FKN, and the pro-inflammatory cytokines tumor necrosis alfa (TNF-alpha) and interleukin 1 beta (IL-1 beta) by enzymelinked immunosorbent assay (ELISA). The antigen-induced arthritis in the TMJ significantly increased the protein levels of P2X7, CatS, FKN, TNF-alpha and IL-1 beta in the trigeminal subnucleus caudalis (P < 0.05). The intra-TMJ injection of BoNT/A reduced the protein levels of P2X7 in all time points tested. Additionally, BoNT/A significantly reduced the protein levels of CatS, FKN, and TNF-alpha 14 days after treatment. However, IL-1 beta was significantly reduced just 24 h after the BoNT/A intra-TMJ treatment. Based on our results, we can suggest that the intra-TMJ injection of BoNT/A may promote a central effect by reducing the P2X7/CatS/FKN microglia-activated pathway in the trigeminal subnucleus caudalis. (AU)

• Processo FAPESP: 17/07741-7 - Efeitos da aplicação periférica de Toxina botulínica A sobre a sensibilização central induzida por artrite na ATM de ratos
• Beneficiário: Victor Ricardo Manuel Muñoz Lora
• Modalidade de apoio: Bolsas no Brasil - Doutorado