• Victor Ricardo Manuel Muñoz-Lora, Henrique Ballassini Abdalla, Del Bel CuryAltair AntoninhaAADepartment of Prosthodontics and Periodontology, Piracicaba Dental School, University of Campinas - UNICAMP, Piracicaba, SP, Brazil. Electronic address: altair@unicamp.br., and Juliana Trindade Clemente-Napimoga.
• Department of Prosthodontics and Periodontology, Piracicaba Dental School, University of Campinas - UNICAMP, Piracicaba, SP, Brazil; Dental Research Division, School of Dentistry, Ibirapuera University, SP, Brazil.
• Toxicon. 2020 Nov 1; 187: 116-121.

AbstractAnalgesic 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 neuromodulators 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 μg/TMJ/week) for 3 weeks. Then, animals were treated with an intra-TMJ injection of BoNT/A (onabotulinumtoxinA, Allergan®; 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 microglial modulators CatS, FKN, and the pro-inflammatory cytokines tumor necrosis alfa (TNF-α) and interleukin 1β (IL-1β) by enzyme-linked immunosorbent assay (ELISA). The antigen-induced arthritis in the TMJ significantly increased the protein levels of P2X7, CatS, FKN, TNF-α and IL-1β 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-α 14 days after treatment. However, IL-1β 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.Copyright © 2020 Elsevier Ltd. All rights reserved.

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