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| Author(s): |
Víctor Ricardo Manuel Muñoz Lora
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Piracicaba, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Faculdade de Odontologia de Piracicaba |
| Defense date: | 2020-02-19 |
| Examining board members: |
Altair Antoninha Del Bel Cury;
Juliana Trindade Clemente Napimoga;
Zdravko Lackovic;
Maria Beatriz Duarte Gavião;
Yuri Martins Costa
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| Advisor: | Altair Antoninha Del Bel Cury |
| Abstract | |
Botulinum toxin type A (BoNT/A) is a neurotoxin produced by the bacterium clostridium botulinum. Currently, BoNT/A is used worldwide in different medical areas, including dentistry. Despite numerous clinical studies demonstrating the therapeutic and adverse effects of BoNT/A in dentistry, so far, the only approval is sialorrhea. Numerous studies showed that the analgesic effect of BoNT / A is, at least in part, of central origin and requires retrograde axonal transport from periphery to central nervous system. On the other hand, its central analgesic mechanism is still unknown. Authors have suggested an action of BoNT/A on glial cells, specifically microglial cells, acting on the glia-neuron communication. For these reasons, we present a critical review exploring the current knowledge about BoNT/A mechanisms of action and effectiveness in disorders related to dentistry; we explore the central transport and neuronal effect of the neurotoxin; and the effect of peripheral applications of BoNT/A on the neuron-glia cross-talk. To achieve the proposed goals, a literature review was performed describing the clinical applications of BoNT/A in dentistry. In addition, two in-vivo experiments using an antigen-evoked persistent pain model in the TMJ of rats were conducted. After induction of TMJ-pain in rats, intra-articular (TMJ) treatments using BoNT/A were applied on animals. Behavioral tests were performed to evaluate the analgesic activity of the toxin, and animals were sacrificed to collect samples and different biochemical tests in the central sensitive regions corresponding to the trigeminal area (trigeminal nucleus caudalis) were conducted. After a critical review of the available literature, we found that BoNT/A can be considered effective for the treatment of trigeminal neuralgia and probably effective for the treatment of temporomandibular disorders. The results of the in-vivo experiments indicate that the antinociceptive effect of BoNT/A depends, in part, on its ability to axonally transport to upper sensory regions (trigeminal nucleus caudalis) and reduce central neuronal activation. Additionally, BoNT/A is able to reduce the levels of Cathepsin S, Fractalcin, IL-1b and TNF-a, possibly acting on the P2X7/Cathepsin S/Fractalkine microglia-activated pathway. Considering all data, we concluded that BoNT/A possess a direct central antinociceptive mechanism that may be associated with a decrease in neuronal activation and a possible action in the glia-neuron communication. This analgesic effect has placed the toxin as a widely used therapeutic tool in dentistry. However, further studies are needed to better describe the long-lasting analgesic effects of BoNT/A (AU) | |
| FAPESP's process: | 17/07741-7 - EFFECTS OF BONT-A PERIPHERAL-APPLICATION ON CENTRAL SENSITIZATION IN TMJ OF RATS |
| Grantee: | Victor Ricardo Manuel Muñoz Lora |
| Support Opportunities: | Scholarships in Brazil - Doctorate |