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Doctoral Thesis
DOI
10.11606/T.42.2015.tde-09122015-064117
Document
Author
Full name
Elaine Flamia Toniolo
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2015
Supervisor
Committee
Dale, Camila Squarzoni (President)
Brigatte, Patrícia
Cury, Yara
Giorgi, Renata
Torrão, Andréa da Silva
Title in Portuguese
Caracterização da hemopressina (agonista inverso de receptores canabinóides do tipo 1) na neuropatia diabética experimental.
Keywords in Portuguese
Dor
Hemopressina
Neuropatia diabética
Receptores CB1
Abstract in Portuguese
A neuropatia periférica diabética é caracterizada por hiperalgesia e alodínia. O receptor CB1 é o principal responsável pelo efeito dos canabinóides na via nociceptiva. A Hemopressina (Hp), é um agonista inverso do CB1, que induz antinocicepção. Neste trabalho investigamos o efeito do tratamento com Hp (2,5 mg/Kg, por 28 dias) sobre a neuropatia diabética de camundongos, induzido por estreptozotocina (200mg/kg). A Hp reverte a hipersensibilidade mecânica em camundongos com neuropatia diabética, sendo que este efeito é específico para o tratamento da nocicepção e envolve a participação de receptores CB1, astrócitos e microglia em nível espinal. A Hp também previne a desmielinização do nervo isquiático dos animais diabéticos, e auxilia na manutenção dos níveis do NGF. Ainda, a Hp participa no controle da sensibilidade ao estímulo térmico quente em animais KO MOR e participa do controle da sensibilidade mecânica de animais KO MOR diabéticos pelo aumento da dimerização de CB1-DOR na medula espinal. Revelando a Hp um candidato para fins terapêuticos.
Title in English
Characterization of hemopressin (inverse agonist of the cannabinoid receptor type 1) in experimental diabetic neuropathy.
Keywords in English
CB1 receptors
Diabetic neuropathy
Hemopressin
Pain
Abstract in English
Diabetic peripheral neuropathy is characterized by hyperalgesia and allodynia. CB1 receptors are primarily responsible for the effect of cannabinoids in nociceptive pathways. Hemopressin (Hp) is an inverse agonist of CB1, which induces antinociception. In this study we investigated the effects of treatment with Hp (2.5 mg / kg for 28 days) on mice subjected to diabetic neuropathy by streptozotocin (STZ - 200 mg/kg). Hp treatement reversed the mechanical hypersensitivity in mice with neuropathy diabetic, and this effect is specific for the treatment of nociception and involves the participation of CB1 receptors, astrocytes and microglia at the spinal level. Hp prevented demyelination of the sciatic nerve in diabetic animals, and assisted in mantaining the levels of NGF. Also, Hp participates in the control of heat sensitivity to thermal stimulus in KO MOR animals and participates in the control of mechanical sensitivity in KO MOR diabetics animals by the increase in CB1-DOR dimerization in the spinal cord. Revealing Hp as a candidate for therapeutic purposes.
 
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Publishing Date
2015-12-09
 
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