RESUMO
Under stressful conditions, the hypothalamic-pituitary-adrenal (HPA) axis acts to promote transitory physiological adaptations that are often resolved after the stressful stimulus is no longer present. In addition to corticosteroids (e.g., cortisol), the neurosteroid allopregnanolone (3α,5α-tetrahydroprogesterone, 3α-hydroxy-5α-pregnan-20-one) participates in negative feedback mechanisms that restore homeostasis. Chronic, repeated exposure to stress impairs the responsivity of the HPA axis and dampens allopregnanolone levels, participating in the etiopathology of psychiatric disorders, such as major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). MDD and PTSD patients present abnormalities in the HPA axis regulation, such as altered cortisol levels or failure to suppress cortisol release in the dexamethasone suppression test. Herein, we review the neurophysiological role of allopregnanolone both as a potent and positive GABAergic neuromodulator but also in its capacity of inhibiting the HPA axis. The allopregnanolone function in the mechanisms that recapitulate stress-induced pathophysiology, including MDD and PTSD, and its potential as both a treatment target and as a biomarker for these disorders is discussed.
Assuntos
Transtorno Depressivo Maior/fisiopatologia , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Pregnanolona/fisiologia , Adaptação Fisiológica , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Doença Crônica , Corticosterona/metabolismo , Transtorno Depressivo Maior/tratamento farmacológico , Retroalimentação Fisiológica , Feminino , Agonistas de Receptores de GABA-A/uso terapêutico , Humanos , Masculino , Modelos Biológicos , Pregnanolona/biossíntese , Receptores de GABA-A/fisiologia , Caracteres Sexuais , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Estresse Fisiológico , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologia , Ácido gama-Aminobutírico/fisiologiaRESUMO
ABSTRACTBACKGROUND AND OBJECTIVES: The status migrainosus is a complication of migraine characterized by severe headache for more than 72 h that did not respond to treatment, with risk of stroke and suicide. Researches on treatment are directed to drugs that stimulate GABA receptors; propofol and isoflurane act on sub-GABAa receptors and theoretically could be interesting. The first has been the subject of research in severe migraine. Opioids are employed in pain, and its use in chronic headache is debatable, but these agents are employed in acute cases. The goal is to present a case of refractory status migrainosus in that we decided to break the pain cycle by general anesthesia.CASE REPORT: Female patient, aged 50 years, with status migrainosus, in the last five days with visits to the emergency department, medicated parenterally with various agents without result. Without comorbidities, dehydrated, described her pain as "well over 10" in Visual Numeric Scale (VNS). After consulting the literature, and given the apparent severity of the condition, we opted for a general anesthesia: induction with fentanyl, propofol, and vecuronium and maintenance with isoflurane and propofol for two hours. Following the treatment, in the postanesthetic recuperation (PAR), the patient related her pain as VNS 3, and was released after five hours with VNS 2. Subsequently, her preventive treatment was resumed.CONCLUSION: Status migrainosus is a rare disabling complication and anesthetics have been the subject of research in its treatment; the option for general anesthesia with agents that stimulate GABA receptors, propofol and isoflurane, in association with fentanyl, proved effective and should encourage new research.
RESUMOJUSTIFICATIVA E OBJETIVOS: O estado de mal-enxaquecoso é complicação da migrânea caracterizada por cefaleia severa por mais de 72 horas não responsiva à terapêutica com risco de AVC e suicídio. Pesquisas no tratamento se direcionam às drogas que estimulam receptores GABA; propofol e isoflurano atuam nos sub-receptores GABAa e teoricamente poderiam ser interessantes. O primeiro já foi objeto de pesquisas na migrânea severa. Opioides são empregados em dor, seu uso crônico nas cefaleias é discutível, mas são empregados nos casos agudos. O objetivo é apresentar caso de estado de mal-enxaquecoso refratário em que se optou para quebrar o ciclo álgico por uma anestesia geral.RELATO DE CASO: Paciente do sexo feminino com 50 anos em estado de mal-enxaquecoso havia cinco dias com passagens anteriores por serviço de urgências, medicada por via parenteral com vários agentes sem resultado. Sem comorbidades, desidratada, descrevia sua dor como "muito superior a 10" na ENV. Após consulta à literatura, face à gravidade aparente do quadro, optou-se pela feitura de uma anestesia geral; a indução foi com fentanil, propofol, vecurônio e manutenção com isoflurano e propofol por duas horas. No fim, na RPA, no primeiro contato classificou sua dor com ENV 3, teve alta após cinco horas com ENV 2. Ulteriormente retomou seu tratamento preventivo.CONCLUSÃO: O mal-enxaquecoso é uma complicação rara incapacitante e anestésicos têm sido objeto de pesquisas no tratamento; a opção por uma anestesia geral com agentes que estimulam os receptores GABA, propofol e isoflurano, aliados ao fentanil, mostrou-se eficaz e deve incentivar pesquisas.
Assuntos
Humanos , Feminino , Anestesia Geral , Transtornos de Enxaqueca/terapia , Medição da Dor , Agonistas de Receptores de GABA-A/uso terapêutico , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND OBJECTIVES: The status migrainosus is a complication of migraine characterized by severe headache for more than 72h that did not respond to treatment, with risk of stroke and suicide. Researches on treatment are directed to drugs that stimulate GABA receptors; propofol and isoflurane act on sub-GABAa receptors and theoretically could be interesting. The first has been the subject of research in severe migraine. Opioids are employed in pain, and its use in chronic headache is debatable, but these agents are employed in acute cases. The goal is to present a case of refractory status migrainosus in that we decided to break the pain cycle by general anesthesia. CASE REPORT: Female patient, aged 50 years, with status migrainosus, in the last five days with visits to the emergency department, medicated parenterally with various agents without result. Without comorbidities, dehydrated, described her pain as "well over 10" in Visual Numeric Scale (VNS). After consulting the literature, and given the apparent severity of the condition, we opted for a general anesthesia: induction with fentanyl, propofol, and vecuronium and maintenance with isoflurane and propofol for two hours. Following the treatment, in the postanesthetic recuperation (PAR), the patient related her pain as VNS 3, and was released after five hours with VNS 2. Subsequently, her preventive treatment was resumed. CONCLUSION: Status migrainosus is a rare disabling complication and anesthetics have been the subject of research in its treatment; the option for general anesthesia with agents that stimulate GABA receptors, propofol and isoflurane, in association with fentanyl, proved effective and should encourage new research.
Assuntos
Anestesia Geral , Transtornos de Enxaqueca/terapia , Feminino , Agonistas de Receptores de GABA-A/uso terapêutico , Humanos , Pessoa de Meia-Idade , Medição da DorRESUMO
INTRODUCTION: Zolpidem is a non-benzodiazepine drug used for the therapy of insomnia, which has selectivity for stimulating the effect of GABA-A receptors. Recently, a paradoxical arousing effect of zolpidem in patients with severe brain damage has been repeatedly reported. METHODS: A placebo-controlled magnetic resonance study was conducted to evaluate its effect on BOLD and metabolites spectral signals in a patient with severe brain injuries and an age-matched healthy volunteer. A multi-modal analysis was used to assess aspects in the pharmacologically-induced changes in the resting-state brain metabolism. RESULTS: A significantly increased BOLD signal was transiently localized in the left frontal cortices, bilateral anterior cingulated areas, left thalamus and right head of the caudate nucleus. The healthy subject showed a deactivation of the frontal, parietal and temporal cortices. BOLD signal changes were found to significantly correlate with concentrations of extravascular metabolites in the left frontal cortex. It is discussed that, when zolpidem attaches to modified GABA receptors of neurodormant brain cells, brain activation is induced. This might explain the significant correlations of BOLD signal changes and proton-MRS metabolites in this patient after zolpidem. CONCLUSION: It was concluded that proton-MRS and BOLD signal assessment could be used to study zolpidem-induced metabolic modulation in a resting state.