Defining the forebrain neurophysiological representation of pain

定义疼痛的前脑神经生理学表征

• 批准号: 10592206
• 负责人: Sharona Ben-Haim
• 金额: $ 19.56万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-01 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10592206
• 关键词: Adult; Affective; Amygdaloid structure; Anatomy; Animals; Anterior; Attenuated; Award; Biological Markers; Biometry; Brain; Brain region; Cerebrum; Chronic; Clinical; Clinical Research; Clinical Trials Design; Cognitive; Complex; Conventional Surgery; Coupling; Data; Deep Brain Stimulation; Development; Development Plans; Diagnosis; Dimensions; Double-Blind Method; Electrodes; Electroencephalography; Electrophysiology (science); Emotional; Epidemiologic Methods; Epilepsy; FDA approved; Foundations; Frequencies; Functional Imaging; Future; Goals; Human; Hybrids; Implant; Implanted Electrodes; Insula of Reil; Intervention; Intractable Pain; Link; Literature; Measures; Medical; Mentors; Methods; Modality; Modeling; Monitor; Neurobiology; Nociception; Operative Surgical Procedures; Opioid; Pain; Pain Measurement; Pain management; Pathway interactions; Patient Self-Report; Patients; Persons; Phase; Physiology; Postoperative Pain; Prefrontal Cortex; Prosencephalon; Psychophysics; Questionnaire Designs; Research; Resolution; Sampling; Sensory; Signal Transduction; Site; Societies; Specific qualifier value; Specificity; Surgical Management; Techniques; Technology; Testing; Therapeutic; Training; Translating; United States; Variant; Work; animal pain; archived data; career; career development; chronic pain; chronic pain management; chronic pain patient; chronic painful condition; cingulate gyrus; clinical pain; cohort; design; effective therapy; experience; implantation; improved; innovation; neural; neural circuit; neuromechanism; neurophysiology; neuroregulation; neurosurgery; novel; opioid epidemic; pain perception; pain processing; pain reduction; pain relief; patient subsets; predictive marker; pressure; prospective

ABSTRACT A significant portion of patients in the United States will suffer from chronic pain at some point in their lives, and for a portion of these patients, our current medical and surgical options are inadequate. Novel treatments aimed at stimulating cerebral circuits involved in nociception for clinical pain relief are promising, but require further development of both targeting and stimulation strategies. Yet, the neural mechanisms of how human nociception manifests as the perception of pain in cerebral circuits remains poorly understood. This proposal leverages neurophysiological access to cortical and subcortical targets in patients undergoing the placement of intracranial EEG electrodes to characterize pain networks in the human brain with specific access to the less often studied nodes in the “pain network” thought to be associated with the emotional and cognitive spheres of pain processing, including the prefrontal cortex, amygdala, insula, and anterior cingulate regions. This unique access will allow detailed exploration of the pain experience in a naturalistic setting based on patients’ self- reported measures of post surgical pain, which will then be contrasted with opiate induced pain reduction. The subset of patients with pre-existing chronic pain conditions will be analyzed for variation in the biomarker signal. Our preliminary findings have yielded two overarching hypotheses: 1) periods of self-reported post- surgical pain will be associated with reduced beta power in prefrontal cortex, an association that will be reversed by the administration of opioids associated with pain relief and 2) the subset of patients with pre- existing chronic pain conditions will have predictable variance, with increases in baseline high beta/low gamma signal compared to patients without chronic pain. Through the use of novel clinical-research hybrid electrodes that allow for targeted, high-resolution electrophysiological recordings, candidate target regions will then be stimulated in an effort to re-create the associated pain reduced state electrophysiologically and clinically. This unique access into human pain circuits will guide further understanding of the physiology of these neural signatures and advance the long-term goal of developing novel paradigms to therapeutically modulate cerebral circuits for the treatment of chronic, intractable pain. This mentored award will provide critical and tailored training in 1) advanced aspects of neurophysiology 2) human experimental and clinical trial design, 3) rigorous epidemiological methods, 4) advanced biostatistics, and 5) validated psychophysical methods for the assessment of pain under the direction of Dr. Eric Halgren, a leading human neurophysiologist. A complementary team of co-mentors, advisors, and consultants has been assembled, including Mary Heinricher, a leader in the field of human and animal pain modulation, Terry Sejnowski, a pioneer in the field of theoretical neurobiology, Mark Wallace, an expert in the field of adult pain management, and Fadel Zeidan, an expert in the functional imaging of pain pathways in humans. The proposed research alongside a detailed career-development plan will facilitate an improved understanding of the anatomical and electrophysiological substrates of human pain, and lay the foundation for a successful transition towards an independent research career focused on the data-driven advancement of neurosurgical therapeutic modalities for chronic pain.

抽象的 美国很大一部分患者在生活中的某个时刻会遭受慢性疼痛， 对于这些患者的一部分，我们目前的医疗和手术选择不足。新颖的治疗方法 旨在刺激涉及伤害感受临床疼痛的脑回路是有希望的，但需要 进一步发展目标和刺激策略。然而，人类如何的神经机制 当脑回路的疼痛感知仍然很少了解时，伤害感受是表现出来的。这个建议 在接受放置的患者中，利用神经生理学获取皮质和皮质下靶标 颅内脑电图电极以表征人脑中的疼痛网络，特异性访问较少 经常在“疼痛网络”中研究与情感和认知领域有关的节点 疼痛加工，包括前额叶皮层，杏仁核，岛状和前扣带回区域。这个独特 访问将根据患者的自我自然环境详细探讨自然主义环境中的疼痛经历 报道了手术后疼痛的度量，然后将其与扩大的诱导疼痛减轻形成对比。这 将分析患有慢性疼痛状况的患者子集的生物标志物变异 信号。我们的初步发现提出了两个总体假设：1） 手术疼痛将与前额叶皮层中的β功率降低有关，这种关联将是 通过与疼痛缓解相关的阿片类药物的给药和2）预先患者的子群的反转 现有的慢性疼痛状况将具有可预测的差异，基线高β/低伽玛的增加 与没有慢性疼痛的患者相比。通过使用新型临床研究混合电极 这允许有针对性的高分辨率电生理记录，候选目标区域将是 刺激以重新产生相关的疼痛在电生理学上和临床上减少了状态。这 独特进入人类疼痛电路的通道将指导对这些神经元生理的进一步了解 签名并促进了开发新型范式进行热调节大脑的长期目标 用于治疗慢性，顽固疼痛的电路。 该修订奖将在1）神经生理学的高级方面提供关键和量身定制的培训 2）人类实验和临床试验设计，3）严格的流行病学方法，4） 生物统计学和5）在指导下评估疼痛的验证心理物理方法 埃里克·哈格伦（Eric Halgren）博士，主要人类神经生理学家。一个完整的联合顾问，顾问， 和顾问已经组装了，包括人类领域的领导人玛丽·海因里希尔（Mary Heinricher） 动物疼痛调制，特里·塞诺夫斯基（Terry Sejnowski），理论神经生物学领域的先驱，马克·华莱士（Mark Wallace）， 成人疼痛管理领域的专家和疼痛功能成像专家Fadel Zeidan 人类的途径。拟议的研究以及详细的职业发展计划将有助于 对人类疼痛的解剖学和电生理底物有了改进的了解，并放置 成功过渡到独立研究职业的基金会，专注于数据驱动 慢性疼痛的神经外科治疗方式的发展。