Neural basis of learned food aversion and nausea

习得性食物厌恶和恶心的神经基础

基本信息

批准号：
7239564
负责人：
Charles Christopher Horn
金额：
$ 23.33万
依托单位：
MONELL CHEMICAL SENSES CENTER
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-06-01 至 2009-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7239564
关键词：
Abdomen Address Affect Agonist Animals Anorexia Nervosa Behavior Brain Brain Stem CNR1 gene Cell Nucleus Cells Chemotherapy-Oncologic Procedure Chronic Chronic Disease Cisplatin Clinical Cytotoxic Chemotherapy Dependence Desire for food Detection Disease Dyspepsia Eating Fiber Food Aversion Human Immunohistochemistry Intestinal Obstruction Intestines Label Lead Learning Lesion Lithium Chloride Location Malignant Neoplasms Maps Mechanics Nausea Nausea and Vomiting Nerve Nerve Fibers Neural Pathways Neuraxis Neurotransmitter Receptor Nucleus solitarius Numbers Pathway interactions Patients Peripheral Peripheral Nerves Pharmaceutical Preparations Physiology Play Property Quality of life Recovery Role Route Sensory Serotonin Serotonin Antagonists Site Spinal Spinal Cord Spinal nerve structure Staining method Stains Stomach Stretch Receptors Stretching Structure of area postrema Substance P Substance P Receptor Techniques Testing Toxin Visceral Vomiting afferent nerve base chemotherapy diabetic gastroparesis dorsal horn gastrointestinal improved nerve supply neurochemistry neurophysiology novel receptor relating to nervous system research study response spinal pathway visceral afferent nerve

项目摘要

DESCRIPTION (provided by applicant): Some medications produce nausea and vomiting that may lead to loss of appetite and reduced food intake, which can negatively affect recovery from disease. Nausea and vomiting are frequently observed with use of cytotoxic chemotherapy agents. Little is known about the neural pathways and mechanism for detecting toxins. Gastrointestinal (GI) sensory nerve fibers play an important role in the initiation of vomiting, and may also be involved in the stimulation of nausea. The present proposal will focus on identifying the pathways and neurochemistry of GI vagal and spinal afferent fibers and brain nuclei that are activated by toxins. To address this issue experiments will be conducted to examine the effects of cisplatin (a chemotherapy agent) and lithium chloride (LiCI) (treatments that produce nausea in humans) on visceral afferent nerve activity and brain and spinal cord Fos expression. Studies will determine: (1) the properties (neurotransmitter receptors, stretch-sensitivity, site of innervation in the stomach and intestine) of vagal and spinal afferent fibers responsive to cisplatin and LiCI using a novel application of single-unit neurophysiology, (2) the brainstem and spinal cord sites that are activated by cisplatin and LiCI treatment using Fos expression, (3) the peripheral neural pathways involved in brain Fos expression produced by cisplatin and LiCI using lesions of the vagus and GI spinal nerves, and (4) the neurotransmitter receptors that play a role in the brain Fos response produced by cisplatin and LiCI treatment. An understanding of the physiology of toxin detection may contribute to nausea treatment in a large number of clinical situations, including cancer chemotherapy, diabetic gastroparesis, anorexia nervosa, ischemic gastropathy, chronic intestinal obstruction, abdominal malignancy, and functional dyspepsia. Effective treatment of nausea may substantially improve the quality of life for patients with chronic disease.

描述（由申请人提供）：某些药物会引起恶心和呕吐，可能导致食欲不振和食物摄入量减少，从而对疾病的康复产生负面影响。使用细胞毒性化疗药物时经常观察到恶心和呕吐。人们对检测毒素的神经通路和机制知之甚少。胃肠道 (GI) 感觉神经纤维在呕吐的引发中发挥着重要作用，也可能参与恶心的刺激。目前的提案将侧重于确定被毒素激活的胃肠道迷走神经和脊髓传入纤维以及脑核的通路和神经化学。为了解决这个问题，我们将进行实验来检查顺铂（一种化疗药物）和氯化锂（LiCI）（引起人类恶心的治疗方法）对内脏传入神经活动以及大脑和脊髓 Fos 表达的影响。研究将确定：(1) 使用单单元神经生理学的新应用来确定对顺铂和 LiCI 敏感的迷走神经和脊髓传入纤维的特性（神经递质受体、拉伸敏感性、胃和肠的神经支配部位），(2)使用 Fos 表达通过顺铂和 LiCI 治疗激活的脑干和脊髓位点，(3) 顺铂和 LiCI 产生的参与脑 Fos 表达的周围神经通路利用迷走神经和胃肠道脊髓神经的损伤，以及（4）在顺铂和LiCI治疗产生的大脑Fos反应中发挥作用的神经递质受体。了解毒素检测的生理学可能有助于许多临床情况下的恶心治疗，包括癌症化疗、糖尿病性胃轻瘫、神经性厌食症、缺血性胃病、慢性肠梗阻、腹部恶性肿瘤和功能性消化不良。有效治疗恶心可以显着改善慢性病患者的生活质量。