Altered Sensibility Following Peripheral Nerve Damage

周围神经损伤后敏感性改变

• 批准号: 7993414
• 负责人: CLIFFORD J WOOLF
• 金额: $ 14.79万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-05 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7993414
• 关键词: Acetone; Acute; Acute Pain; Afferent Neurons; Animals; Area; Biological Models; Body Temperature; Brain; Capsaicin; Chemicals; Chronic; Clinical; Collaborations; Development; Formalin; Frequencies; Freund' s Adjuvant; Future; Gene Expression; Genes; Hour; Implant; Injury; Intractable Pain; Laboratories; Maintenance; Measures; Mechanics; Modality; Modeling; Molecular; Monitor; Motor Activity; Mus; Nerve; Nervous system structure; Neurobiology; Neuronal Plasticity; Neurons; Nociception; Pain; Peripheral; Peripheral Nerves; Peripheral nerve injury; Phenotype; Pilot Projects; Polysomnography; Procedures; REM Sleep; Regulation; Resistance; Risk Factors; Severities; Sleep; Sleep Architecture; Sleep Deprivation; Sleep Fragmentations; Spinal Ganglia; Spinal cord posterior horn; Subcutaneous Injections; Synaptic Transmission; System; Telemetry; Testing; Time; base; chronic pain; design; inflammatory neuropathic pain; inflammatory pain; injured; mouse model; mustard oil; nerve injury; pain behavior; painful neuropathy; parent grant; public health relevance; research study; spontaneous pain; tool; transcription factor; vigilance

DESCRIPTION (provided by applicant): The parent grant is devoted to studying the mechanisms responsible for peripheral neuropathic pain. Peripheral axonal injury changes the expression of hundreds of genes in dorsal root ganglion neurons, including many that contribute to neuropathic pain, by increasing the excitability of the injured neurons and by altering their synaptic transmission and connectivity in the dorsal horn of the spinal cord. In the parent grant, we are studying the regulation of "pain-contributing" genes and their orchestration by induction of master regulator transcription factors. For the competitive revision we now wish to pursue two completely new questions: Does pain alter sleep architecture, and does sleep deprivation alter pain sensitivity and chronicity? Our overall hypothesis is that the neural plasticity intrinsic to pain and sleep converge, and in consequence the two phenomena are not independent. We predict that pain will alter sleep and that sleep deprivation will alter pain, and we plan pilot experiments to test this. Furthermore, we predict that the changes in sleep produced by pain may alter the transition of acute to chronic pain by generating maladaptive plasticity in the brain. PUBLIC HEALTH RELEVANCE: Peripheral nerve injury can result in severe intractable pain, resistant to most forms of therapy (peripheral neuropathic pain). The studies in the parent grant are designed to determine how changes in gene expression in sensory neurons after nerve damage are orchestrated and act to produce long-term changes in the function and structure of the nervous system. For the competitive revision we will collaborate with Dr Tom Scammell, a world expert on sleep, to explore in mouse models if chronic inflammatory and neuropathic pain alters sleep, and the reverse to determine if sleep deprivation alters acute pain sensitivity and the severity and chronicity of inflammatory and neuropathic pain.

描述（由申请人提供）：父母补助金致力于研究周围神经性疼痛的机制。外周轴突损伤通过增加受损神经元的兴奋性和通过改变它们在脊髓背角中的突触传递和连接性来改变背根神经节神经元中数百个基因的表达，包括许多导致神经性疼痛的基因。在家长补助金，我们正在研究的“疼痛贡献”基因的调控和他们的编排诱导主调节转录因子。对于竞争性修订，我们现在希望追求两个全新的问题：疼痛是否会改变睡眠结构，睡眠剥夺是否会改变疼痛的敏感性和慢性性？我们的总体假设是，疼痛和睡眠内在的神经可塑性收敛，因此这两种现象不是独立的。我们预测疼痛会改变睡眠，而睡眠剥夺会改变疼痛，我们计划进行试点实验来验证这一点。此外，我们预测，疼痛引起的睡眠变化可能会通过在大脑中产生适应不良的可塑性来改变急性疼痛向慢性疼痛的过渡。 公共卫生关系：周围神经损伤可导致严重的顽固性疼痛，对大多数形式的治疗都有抵抗力（周围神经性疼痛）。父母补助金中的研究旨在确定神经损伤后感觉神经元中基因表达的变化如何协调并产生神经系统功能和结构的长期变化。对于竞争性修订，我们将与世界睡眠专家Tom Scammell博士合作，在小鼠模型中探索慢性炎症和神经性疼痛是否会改变睡眠，以及相反的情况，以确定睡眠剥夺是否会改变急性疼痛敏感性以及炎症和神经性疼痛的严重性和慢性性。