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 美国有相当多的患者在一生中的某个时刻会遭受慢性疼痛的困扰， 对于其中一部分患者，我们目前的医疗和手术选择还不够。 针对参与伤害感受的脑刺激回路来缓解临床疼痛是有希望的，但需要 然而，人类如何进一步发展靶向和刺激策略。 伤害感受表现为大脑回路中的疼痛感知。这一提议仍然知之甚少。 利用神经生理学途径接触接受植入的患者的皮质和皮质下目标 颅内脑电图电极可表征人脑中的疼痛网络，并可特定访问较少的区域 经常研究“疼痛网络”中的节点，这些节点被认为与情感和认知领域相关 疼痛处理包括前额皮质、杏仁核、岛叶和前扣带回区域。 访问将允许在基于患者自我的自然环境中详细探索疼痛体验 报告了手术后疼痛的测量结果，然后将其与阿片类药物引起的疼痛减轻进行对比。 将分析预先存在慢性疼痛状况的患者子集的生物标志物变化 我们的初步研究结果得出了两个总体假设：1）自我报告的后期阶段。 手术疼痛将与前额皮质β功率降低有关，这种关联将 通过给予与疼痛缓解相关的阿片类药物来逆转，2) 患有前期症状的患者子集 现有的慢性疼痛状况将具有可预测的差异，基线高贝塔/低伽马值会增加 通过使用新型临床研究混合电极与没有慢性疼痛的患者进行比较。 允许有针对性的高分辨率电生理记录，然后将候选目标区域 刺激以努力在电生理学和临床上重建相关的疼痛减轻状态。 对人类疼痛回路的独特了解将指导进一步了解这些神经的生理学 特征并推进开发新范例来治疗调节大脑的长期目标 用于治疗慢性顽固性疼痛的电路。 该指导奖项将在 1) 神经生理学的高级方面提供关键和定制的培训 2）人体实验和临床试验设计，3）严格的流行病学方法，4）先进 生物统计学，以及5）经过验证的心理物理学方法，用于在指导下评估疼痛 埃里克·哈尔格伦 (Eric Halgren) 博士是一位领先的人类神经生理学家，由共同导师、顾问、 和顾问已经聚集在一起，其中包括玛丽·海因里彻（Mary Heinricher），她是人类和环境领域的领导者 动物疼痛调节，Terry Sejnowski，理论神经生物学领域的先驱，Mark Wallace， 成人疼痛管理领域专家和疼痛功能成像专家 Fadel Zeidan 拟议的研究以及详细的职业发展计划将促进 提高了对人类疼痛的解剖学和电生理学基础的理解，并奠定了 为成功过渡到专注于数据驱动的独立研究职业奠定了基础 慢性疼痛的神经外科治疗方式的进展。