Mecanismos envolvidos na hipoalgesia induzida por inibidores seletivos de ciclooxigenase-2 em modelos de inflamação em pata de ratos

• Ano de defesa: 2012
• Autor(a) principal: Dorothea Schmidt Franca
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Opióides; Hipoalgesia; Hiperalgesia; Microtúbulos; Inibidores de COX-2; Farmacologia; Fisiologia
• Link de acesso: http://hdl.handle.net/1843/JNFI-7FSGWN

The aim of this work was elucidated the mechanism involved in hypoalgesic response induced by selective inhibitors of COX-2 (ICOX-2). Hyperalgesia induced by carrageenan (250 g) was modified by pre-treatment with three selective inhibitors of COX-2, celecoxib e SC 236. These inhibitors raised the nociceptive threshold above the normal and was called hypoalgesia. This effect was observed in different strains of rat (Holtzman, Wistar and Sprague-Dawley) and different modes of administration of the inhibitor of COX-2 (locally or systemically). A selective inhibitor of COX-1 SC 560 (1, 5 and 10 mg/Kg) reduced the hyperalgesia, but did not induced hypoalgesia and did not affect paw oedema. The hypoalgesia was induced when the hyperalgesic stimuli was PGE2 (200ng/pata). This results suggested that hypoalgesia did not envolved the synthesis of prostaglandins. Pre-treatment with inhibitors of synthase NO L-NAME e L-NMMA reverted the hyperalgesia and reduced the hypoalgesia, showing the contribution of nitric oxide in this response. The antagonist of opioid receptor naltrexone (3 mg/Kg) did not affect the hyperalgesia induced by carrageenan in control animals, however, abolished the hypoalgesia induced by ICOX-2 celecoxib, rofecoxib, SC 236. The antinociceptive effect of indometacin did not affect by naltrexone. In rats tolerant to the morphine, the hypoalgesic effect by SC 236 was abolished, however the antiniciceptive effect by indometacin and SC 560 were unaffected. In this model of hyperalgesia, the effect hypoalgesic induced by ICOX-2 envolved the participation of endogenous opioids. With the aim to observe if the microtubule was envolved with hypoalgesic, drug which affect microtubule was used. Paclitaxel (taxol), colchicina and nocodazol reverted the hypoalgesia induced by celecoxib. Using imunohistochemistry techniques and confocal microscopic, was observed sensitive neurons (-tubuline) treated with selective or not-selective inhibitors of cyclooxigenases. Was observed points of interruption on prolongaments and reduced of fluorescence in cells treated with ICOX-2, showing that inhibitors probably affect the structure of microtubule and this effect could was relationed with hypoalgesia. We conclude that the hypoalgesic response induced by ICOX-2 was involved endogenous opioids with contribution of nitric oxide. The interaction of coxibs and perturbing agents of microtubules was evidenced.