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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2011.tde-23012012-114018
Document
Author
Full name
Luciana de Britto Pedroso
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2011
Supervisor
Committee
Cury, Yara (President)
Costa, Soraia Kátia Pereira
Cunha, Thiago Mattar
Hayashi, Lia Siguemi Sudo
Tambeli, Claudia Herrera
Title in Portuguese
Avaliação da possível diferença na sensibilidade dolorosa de ratos machos e fêmeas e da resposta de cada sexo a crotalfina, um analgésico tipo opióide.
Keywords in Portuguese
Hormônios sexuais
Ópio
Peptídeos
Ratos
Receptores de droga
Venenos de origem animal
Abstract in Portuguese
Evidências clínicas e experimentais têm sugerido a existência de diferenças na sensação de dor e na resposta a fármacos analgésicos entre machos e fêmeas. A crotalfina (CRF), um peptídeo inicialmente isolado e caracterizado no veneno de serpentes Crotalus durissus terrificus, apresenta efeito antinociceptivo, quando avaliado em diferentes modelos experimentais de dor aguda e crônica. O efeito deste peptídeo é de longa duração e mediado pela ativação de receptores opióides periféricos do tipo k e d. Contudo, os estudos com a crotalfina foram sempre realizados utilizando roedores machos. Assim, o presente projeto de pesquisa teve por objetivo avaliar a diferença na sensibilidade dolorosa e no efeito antinociceptivo da crotalfina, entre ratos machos e fêmeas. Os resultados mostraram que fêmeas apresentam menor limiar nociceptivo e maior sensibilidade à dor. A crotalfina apresentou maior potência antinociceptiva em fêmeas. A diferença na sensibilidade dolorosa e na resposta a analgésicos pode ser decorrente da presença de hormônios esteroidais gonadais.
Title in English
Sex differences in nociception and in the antinociceptive activity of crotalphine, an opioid-like analgesic drug.
Keywords in English
Animal poisons
Drug receptors
Opium
Peptides
Rats
Sex hormones
Abstract in English
Several clinical and experimental evidence have suggested the existence of sex differences in pain sensation and in the analgesic effect of opioid drugs in human and rodents. Crotalphine (CRP), a peptide first characterized in the venom of the South American rattlesnake Crotalus durissus terrificus, displays potent and long-lasting opioid (peripheral k and d opioid receptors) analgesic activity in experimental models of acute and chronic pain. Due to its potent and long-lasting analgesic effect, pre-clinical trials with the synthetic peptide and analogues are now in progress. However, the experimental studies with CRP have always been developed in male animals. This study aims to evaluate the differences in pain sensation and in the analgesic response to CRP between male and female Wistar rats. Sex differences could be observed between male and female rats in relation to pain threshold. However, despite displaying opioid activity, the new analgesic peptide CRP is more effective in females than males. These differences could be related with sex hormones.
 
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Publishing Date
2012-03-16
 
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