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Doctoral Thesis
DOI
10.11606/T.42.2013.tde-26092013-104400
Document
Author
Full name
Vanessa Pacciari Gutierrez
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2013
Supervisor
Committee
Cury, Yara (President)
Brigatte, Patrícia
Dagli, Maria Lucia Zaidan
Picolo, Gisele
Vessoni, Sandra Coccuzzo Sampaio
Title in Portuguese
Efeito antinociceptivo da crotalfina sobre a dor óssea induzida pelo tumor de Walker 256 em fêmur de ratos.
Keywords in Portuguese
Analgésicos
Células cultivadas de tumor
Dor
Fêmur
Neoplasias
Abstract in Portuguese
Neste estudo padronizamos modelo de dor óssea induzida pela administração de células do tumor de Walker 256 em fêmur de ratos e avaliamos o efeito analgésico da crotalfina, um peptídeo com atividade analgésica. Análises radiográficas, tomográficas e cintilográficas demonstraram a presença de processos osteolíticos difusos, destruição do tecido cortical ósseo e intensa atividade osteogênica. Foi detectado aumento de partes moles adjacentes ao osso, fenômeno observado em pacientes com câncer ósseo. Análises histopatológicas mostraram a presença de células tumorais no pulmão, baço e fígado dos animais, indicando disseminação das células tumorais. Foi detectada a presença de hiperalgesia, alodinia e dor manifesta, a partir do 1º dia após a inoculação das células, persistindo por pelo menos 14 dias. Crotalfina (8 mg/kg, p.o) administrada no 14º dia, bloqueou estes fenômenos. Esse efeito antinociceptivo é de longa duração (48 h) e mediado por receptores opióides do tipo k e d. Não foi observado desenvolvimento de tolerância após o tratamento prolongado com crotalfina.
Title in English
Antinociceptive effect of crotalphine in bone pain induced by Walker 256 tumor cells into femoral cavity of rats.
Keywords in English
Analgesics
Cultured tumor cells
Femur
Neoplasms
Pain
Abstract in English
The aim of the present work was to standardize a new rat model of bone pain induced by the injection of Walker 256 carcinoma cells into the femoral cavity of rats, and to evaluate the analgesic effect of crotalphine, an analgesic peptide. Radiographic, tomographic and scintigraphic analysis showed the presence of diffuse osteolytic processes, destruction of cortical bone tissue and intense osteogenic activity. Increase of soft tissue adjacent to the bone was also detected, being this phenomenon observed in patients with bone cancer. Hystopathological analysis showed the presence of tumor cells in lungs, spleen and liver, indicating the occurrence of metastasis. Tumor cell inoculation induced the presence of hyperalgesia, allodynia and spontaneous pain. Crotalphine (8 mg/kg, p.o.), administered on day 14, blocked these phenomena. This antinociceptive effect is long-lasting effect (2 days) and mediated by peripheral k and d- opioid receptors. Prolonged treatment with crotalphine (14 days) did not cause the development of tolerance to its antinociceptive effect.
 
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Publishing Date
2013-12-06
 
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