Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Cephalalgia ; 39(1): 77-90, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29771142

RESUMO

BACKGROUND: Post-traumatic headache is the most common and long-lasting impairment observed following mild traumatic brain injury, and frequently has migraine-like characteristics. The mechanisms underlying progression from mild traumatic brain injury to post-traumatic headache are not fully understood. The aim of this study was to develop a mouse model of post-traumatic headache and identify mechanisms and novel targets associated with this disorder. METHODS: We combined the closed head weight-drop method and the nitroglycerin chronic migraine model. To induce mild traumatic brain injury, a weight was dropped onto intact crania of mildly anesthetized mice, and mechanical responses to chronic-intermittent administration of nitroglycerin, a human migraine trigger, were determined at multiple time points post-injury. RESULTS: Low dose nitroglycerin (0.1 mg/kg) evoked acute periorbital and hind paw allodynia in both mild traumatic brain injury and sham animals. However, only mild traumatic brain injury mice developed chronic hypersensitivity to low dose nitroglycerin. Migraine medications, sumatriptan and topiramate, inhibited post-traumatic headache-associated allodynia. In addition, the delta opioid receptor agonist, SNC80, also blocked post-traumatic headache-associated allodynia. Finally, we examined the expression of calcitonin gene-related peptide within this model and found that it was increased in trigeminal ganglia two weeks post-mild traumatic brain injury. CONCLUSIONS: Overall, we have established a mouse model of post-traumatic headache and identified the delta opioid receptor as a novel therapeutic target for this disorder.


Assuntos
Concussão Encefálica/complicações , Modelos Animais de Doenças , Cefaleia Pós-Traumática/etiologia , Cefaleia Pós-Traumática/metabolismo , Receptores Opioides delta/metabolismo , Animais , Hiperalgesia/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transtornos de Enxaqueca/etiologia , Transtornos de Enxaqueca/metabolismo , Gânglio Trigeminal/metabolismo
2.
Cephalalgia ; 38(8): 1471-1484, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29022756

RESUMO

Background Nitric oxide (NO) has been heavily implicated in migraine. Nitroglycerin is a prototypic NO-donor, and triggers migraine in humans. However, nitroglycerin also induces oxidative/nitrosative stress and is a source of peroxynitrite - factors previously linked with migraine etiology. Soluble guanylyl cyclase (sGC) is the high affinity NO receptor in the body, and the aim of this study was to identify the precise role of sGC in acute and chronic migraine. Methods We developed a novel brain-bioavailable sGC stimulator (VL-102), and tested its hyperalgesic properties in mice. We also determined the effect of VL-102 on c-fos and calcitonin gene related peptide (CGRP) immunoreactivity within the trigeminovascular complex. In addition, we also tested the known sGC inhibitor, ODQ, within the chronic nitroglycerin migraine model. Results VL-102-evoked acute and chronic mechanical cephalic and hind-paw allodynia in a dose-dependent manner, which was blocked by the migraine medications sumatriptan, propranolol, and topiramate. In addition, VL-102 also increased c-fos and CGRP expressing cells within the trigeminovascular complex. Importantly, ODQ completely inhibited acute and chronic hyperalgesia induced by nitroglycerin. ODQ also blocked hyperalgesia already established by chronic nitroglycerin, implicating this pathway in migraine chronicity. Conclusions These results indicate that nitroglycerin causes migraine-related pain through stimulation of the sGC pathway, and that super-activation of this receptor may be an important component for the maintenance of chronic migraine. This work opens the possibility for negative sGC modulators as novel migraine therapies.


Assuntos
Hiperalgesia/induzido quimicamente , Hiperalgesia/enzimologia , Transtornos de Enxaqueca/enzimologia , Guanilil Ciclase Solúvel/fisiologia , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/uso terapêutico , Regulação Alostérica , Animais , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/uso terapêutico , Peptídeo Relacionado com Gene de Calcitonina/biossíntese , Modelos Animais de Doenças , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/uso terapêutico , Feminino , Hiperalgesia/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transtornos de Enxaqueca/induzido quimicamente , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/etiologia , Terapia de Alvo Molecular , Óxido Nítrico/efeitos adversos , Óxido Nítrico/metabolismo , Doadores de Óxido Nítrico/farmacologia , Nitroglicerina/farmacologia , Oxidiazóis/administração & dosagem , Oxidiazóis/metabolismo , Oxidiazóis/uso terapêutico , Propranolol/administração & dosagem , Propranolol/uso terapêutico , Proteínas Proto-Oncogênicas c-fos/biossíntese , Quinoxalinas/administração & dosagem , Quinoxalinas/metabolismo , Quinoxalinas/uso terapêutico , Agonistas do Receptor 5-HT1 de Serotonina/administração & dosagem , Agonistas do Receptor 5-HT1 de Serotonina/uso terapêutico , Guanilil Ciclase Solúvel/metabolismo , Sumatriptana/administração & dosagem , Sumatriptana/uso terapêutico , Topiramato/administração & dosagem , Topiramato/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...