RESUMO
Autonomic nerves are attractive targets for medical therapies using electroceutical devices because of the potential for selective control and few side effects. These devices use novel materials, electrode configurations, stimulation patterns, and closed-loop control to treat heart failure, hypertension, gastrointestinal and bladder diseases, obesity/diabetes, and inflammatory disorders. Critical to progress is a mechanistic understanding of multi-level controls of target organs, disease adaptation, and impact of neuromodulation to restore organ function.
Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Terapia por Estimulação Elétrica/métodos , Cardiopatias/terapia , Animais , Diabetes Mellitus/fisiopatologia , Diabetes Mellitus/terapia , Terapia por Estimulação Elétrica/instrumentação , Gastroenteropatias/fisiopatologia , Gastroenteropatias/terapia , Cardiopatias/fisiopatologia , Humanos , Inflamação/fisiopatologia , Inflamação/terapia , Obesidade/fisiopatologia , Obesidade/terapia , Estimulação da Medula Espinal/instrumentação , Estimulação da Medula Espinal/métodos , Doenças da Bexiga Urinária/fisiopatologia , Doenças da Bexiga Urinária/terapia , Estimulação do Nervo Vago/instrumentação , Estimulação do Nervo Vago/métodosRESUMO
Cancer chemotherapy drugs, such as cisplatin, are extremely potent for producing nausea and vomiting. The acute effects of these treatments are partly controlled using anti-emetic drugs, but the delayed effects (>24 h), especially nausea, are much more difficult to treat. Furthermore, cisplatin induces a long-term (up to 48 h) increase in pica in rats. Pica is manifested as an increase in consumption of kaolin (clay) and is used as a measure of visceral sickness. It is unknown what brain pathways might be responsible for this sickness associated behavior. As a first attempt to define this neural system, rats were injected (i.p.) with 3, 6, or 10 mg/kg cisplatin (doses reported to produce pica) and sacrificed at 6, 24, or 48 h to determine brain Fos expression. The primary results indicate: 1) increasing the dose of cisplatin increased the magnitude and duration of brain Fos expression, 2) most excitatory effects on hindbrain nucleus of the solitary tract (NTS) and area postrema (AP) Fos expression occurred within 24 h after cisplatin injection, 3) 6 and 10 mg/kg cisplatin treatment produced large increases in Fos expression in the central amygdala (CeA) and bed nucleus of the stria terminalis (BNST), including 48 h after injection, and 4) cisplatin treatment produced little effect on Fos expression in the paraventricular and supraoptic nuclei of the hypothalamus. These results indicate that cisplatin activates a neural system that includes the dorsal vagal complex (NTS and AP), CeA, and BNST.