Cortical Signature and Modulation of Pain

皮质特征和疼痛调节

基本信息

批准号：
10210309
负责人：
ZHIGANG HE
金额：
$ 79.26万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-30 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10210309
关键词：
Ablation Acute Affect Affective Anterior Apical Area Attenuated Axon Behavior Brain Cell Nucleus Cells Cognitive Computer Analysis Data Dendrites Development Dimensions Dissection Efferent Pathways Electric Stimulation Electrodes Elements Esthesia Excision Face Fingers Forelimb Foundations Future Genetic Goals Head Headache Human Hypersensitivity Image Individual Injury Knowledge Label Light Link Literature Maps Massage Mechanics Motor Motor Cortex Movement Mus Neurons Nociception Operative Surgical Procedures Pain Pain Disorder Painless Pathway interactions Patients Pattern Perception Physiology Play Population Primary Lesion Process Reporting Research Rodent Role Sensory Slice Somatosensory Cortex Spinal Stimulus Tactile Techniques Testing Thalamic structure Time Tongue Touch sensation Trigeminal Neuralgia allodynia anatomical tracing base brain research central pain chronic neuropathic pain chronic pain chronic pain patient cingulate cortex cingulotomy dorsal horn extracellular imaging study in vivo in vivo calcium imaging inflammatory pain injured mechanical allodynia mouse model negative affect nerve injury nerve supply neural circuit neuroregulation optogenetics pain model pain perception pain processing pain relief pain sensation painful neuropathy pressure presynaptic programs relating to nervous system response sensory cortex somatosensory tissue injury virus genetics zona incerta

项目摘要

Cortical Signature and Modulation of Pain Abstract/Project Summary Pain perception contains two main dimensions: the sensory-discriminative and the affective-cognitive aspects. In this proposal, we will focus on the cortical signature and modulations of the sensory aspects of pain using mouse models. Pain can be largely divided into inflammatory or neuropathic pain. A common condition in both types of pain is mechanical allodynia: externally applied innocuous gentle touch becomes painful. Paradoxically, pain elicits self-initiated recuperative behaviors such as rubbing and massaging of the painful regions; and the mechanical stimuli from such self-generated behaviors generally relieve pain. The neural circuit mechanisms underlying the opposite effects of external versus self-applied mechanical stimuli in pain conditions remain poorly understood. Based on previous research as well as our preliminary studies, we hypothesize that corticospinal projecting neurons from primary somatosensory (S1) cortex facilitate mechanical hypersensitivity in pain models, whereas specific motor cortex projection neurons play key roles in suppressing tactile allodynia in self-initiated recuperative behaviors (such as licking and wiping in mice). We further hypothesize that the cortical pain signature can be read out from activity patterns of large populations of individual S1 neurons by comparing their activities in the painful versus non-painful or pain- relieved conditions. We will use a combination of viral-genetic labeling of specific cortical neurons, in vivo calcium imaging and in vivo multi-electrode extracellular recording in freely behaving mice, optogenetics- assisted slice physiology, opto/chemicogenetic manipulations, and computational analyses to test our hypotheses.

皮质特征和疼痛调节摘要/项目摘要疼痛感知包含两个主要维度：感觉歧视和情感认知方面。在此提案中，我们将重点关注的是皮质的签名和调制的感官方面使用鼠标模型疼痛。疼痛可以很大程度上分为炎症或神经性疼痛。常见两种类型疼痛的状况都是机械异常性痛：外部应用无害的温柔触摸变成痛苦。矛盾的是，疼痛引起了自我引发的恢复行为，例如摩擦和按摩痛苦的地区；这种自我生成的行为的机械刺激通常可以缓解疼痛。这神经电路机制是外部与自我应用机械刺激的相反作用的基础在疼痛条件下，人们的理解仍然很少。根据先前的研究以及我们的初步研究我们假设来自原发性体感（S1）皮质的皮质脊髓投射神经元有助于疼痛模型中的机械性超敏反应，而特定的运动皮层投影神经元起关键作用在抑制自我引发的恢复行为（例如小鼠舔和擦拭）中的触觉异常。我们进一步假设可以从大型活动模式中读取皮质疼痛特征单个S1神经元的种群通过比较其在疼痛与非疼痛或疼痛中的活性缓解条件。我们将结合特定皮质神经元的病毒遗传标记，体内钙成像和体内多电极在自由行为的小鼠中的细胞外记录，光遗传学 - 辅助切片生理学，光学/化学遗传操作和计算分析以测试我们假设。