Avaliação in vitro e in vivo do potencial anestésico da neosaxitoxina em bloqueios perineurais

• Ano de defesa: 2025
• Autor(a) principal: Ribeiro, Matheus Rocha
• Orientador(a): Andrade, Silvia Maria Caldeira Franco
• Banca de defesa: Kanashiro, Gláucia Prada, Nogueira, Rosa Maria Barilli, Cardoso, Guilherme Schiess, Cassu, Renata Navarro
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade do Oeste Paulista
• Programa de Pós-Graduação: Doutorado em Fisiopatologia e Saúde Animal
• Departamento: Doutorado em Meio Ambiente e Desenvolvimento Regional
• País: Brasil
• Palavras-chave em Português: analgesia, anestésicos locais, canina, úlcera de córnea, oftalmologia.
• Palavras-chave em Inglês: analgesia, local anesthetics, locoregional block, canine, corneal ulcer, ophthalmology.
• Área do conhecimento CNPq: CIENCIAS AGRARIAS::MEDICINA VETERINARIA
• Link de acesso: http://bdtd.unoeste.br:8080/jspui/handle/jspui/1716

Neosaxitoxin (NeoSTX) is a potent neurotoxin with long-lasting local anesthetic properties. This study aimed to evaluate the effects of NeoSTX in two distinct experimental models: an in vitro study using a mouse phrenic nerve-diaphragm preparation and a clinical study assessing peribulbar block in dogs. In the first study, eight male Unib:SW mice were euthanized with isoflurane followed by exsanguination. Hemi-diaphragms and their respective phrenic nerves were isolated and mounted in a myographic system containing Tyrode's solution maintained at 37°C and aerated with carbogen (95% O₂ + 5% CO₂). The preparations were tensioned at 1 g/cm² and stimulated with supramaximal pulses (0.1 Hz; 0.2 ms). After stabilization of contractile responses, increasing concentrations of NeoSTX (32 nM, 100 nM, 320 nM, 1 μM, and 3.2 μM) were applied, with responses recorded by an isometric transducer coupled to the LabScribe4 system. In the second study, 22 dogs were randomly allocated into two groups: NeoSTX Group (G-NeoSTX, n=11), receiving 3.5 μg of NeoSTX, and Bupivacaine Group (G-Bupi, n=11), receiving 0.5% bupivacaine (0.2 mL/kg). All animals were premedicated with dexmedetomidine (2 μg/kg IM) and methadone (0.3 mg/kg IM), induced with propofol (effect-dose IV), and maintained with isoflurane/O₂. The peribulbar block was performed immediately after intubation. Cardiorespiratory parameters (heart rate, respiratory rate, SpO₂, ETCO₂, and mean arterial pressure) and end-tidal isoflurane concentration (ETiso) were monitored during the procedure. Pain was assessed using numerical descriptive scales (0-4) before medication (baseline) and at 1, 2, 4, 6, 8, 12, and 24 hours post-extubation. Rescue analgesia (methadone 0.3 mg/kg IM) was administered when necessary. Results showed that in the in vitro study, NeoSTX at 3.2 μM concentration induced complete neuromuscular blockade within 120 minutes, with times to 50% and 90% blockade of 8.8 ± 1.5 minutes and 12.9 ± 2.8 minutes, respectively. In the clinical study, G-NeoSTX exhibited significantly longer analgesia duration (956 ± 202 minutes) compared to G-Bupi (331 ± 59 minutes; p=0.001), lower ETiso values (p=0.0006-0.04), and shorter recovery time (p<0.05), with no significant differences in cardiorespiratory parameters between groups. In conclusion, NeoSTX demonstrated dose-dependent neuromuscular blockade in vitro and provided longer-lasting analgesia in vivo compared to bupivacaine, representing a promising alternative for locoregional anesthesia.