Harnessing cortical neuromodulation to disrupt pain perception

利用皮质神经调节来破坏疼痛感知

• 批准号: 10589454
• 负责人: Gregory Corder
• 金额: $ 16.43万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10589454
• 关键词: Acute; Affective; Amygdaloid structure; Anterior; Area; Attention; Award; Behavior; Brain; Brain Stem; Brain region; Breathing; Cognitive; Dangerousness; Data Analyses; Development; Dimensions; Disease; Emotional; Goals; Impaired cognition; Medical; Methods; Molecular; Negative Valence; Neuroanatomy; Neurobiology; Neurosciences; Nociception; Nociceptive Stimulus; Opioid; Opioid Analgesics; Pain; Parents; Patients; Prefrontal Cortex; Research; Rewards; Role; Route; Sensory; Short-Term Memory; Stimulus; Technology; Thalamic structure; Therapeutic; Therapeutic Effect; Training; Ventilatory Depression; base; career; cell type; chronic pain; chronic pain management; cingulate cortex; directed attention; experimental study; genetic technology; improved; machine vision; mouse genetics; mu opioid receptors; neural circuit; neuroregulation; opioid epidemic; opioid therapy; pain behavior; pain perception; pain processing; pain sensation; prevent; receptor binding; side effect; statistics; virus genetics

PROJECT SUMMARY Chronic pain is characterized by sensory, emotional, and cognitive dysfunction. Some patients on opioid therapies can perceive the negative valence of pain as separate, or “dissociated,” from the sensation of pain. This suggests that altering the affective-attention dimension of pain contributes significantly to the therapeutic effect of opioids. However, opioids have significant negative side effects. Opioids carry addictive and respiratory depression liabilities due to the expression of mu opioid receptors (MORs)—the molecular receptor binding opiates—in reward-related and brainstem breathing areas of the brain. Identifying the nociceptive brain circuits underlying opioid analgesia, separate from those underlying dangerous side effects, is key to developing improved, non-addictive therapeutics for managing chronic pain and combating the Opioid Epidemic. Many brain regions contribute to the emotional and cognitive facets of pain. Importantly, anticipation of pain, acute noxious stimuli, and chronic pain all strongly activate the anterior cingulate cortex (ACC). The function of the ACC in pain processing appears to integrate nociceptive information within working memory to direct attention to and facilitate anticipation of nociceptive stimuli, but it remains unknown how noxious information enters the ACC. In the DP2 parent award, we are currently exploring nociceptive inputs from the amygdala, however, there are other key connective routes of pain-related information into the ACC, such as the midline thalamus (MTh). Here, we extend the parent DP2 studies to investigate the MOR+ MTh projection circuit that innervates nociceptive ACC regions. In Goal 1, we will determine the neuroanatomy of opioidergic nociceptive neural circuits using activity-dependent viral and mouse genetics, and in Goal 2 we will determine the functional role of thalamocortical opioidergic circuits to pain behavior using cell-type specific manipulations and machine- vision based behavior quantification methods, which were developed in the parent DP2 experiments. Completion of the proposed research will facilitate the trainee’s technical mastery of several advanced neuroscience technologies, data analysis and statistics, as well as several training goals to prepare the trainee for a career in pain neurobiology research.

项目摘要 慢性疼痛的特征在于感觉、情绪和认知功能障碍。一些服用阿片类药物的患者 治疗可以将疼痛的负效价感知为与疼痛感觉分离或“分离”。 这表明，改变疼痛的情感注意维度有助于显著的治疗效果。 阿片类药物的作用。然而，阿片类药物具有显著的负面影响。阿片类药物携带成瘾性和呼吸 抑郁倾向由于μ阿片受体（MORs）的表达-分子受体结合 阿片类药物-在大脑的奖励相关区域和脑干呼吸区域。识别伤害性大脑回路 潜在的阿片类镇痛，与那些潜在的危险副作用分开，是发展的关键。 用于管理慢性疼痛和对抗阿片类流行病的改进的非成瘾性疗法。 许多大脑区域都对疼痛的情感和认知方面做出了贡献。重要的是，对疼痛的预期， 急性伤害性刺激和慢性疼痛都强烈激活前扣带皮层（ACC）。的功能 疼痛处理中的ACC似乎将伤害性信息整合到工作记忆中， 注意和促进伤害性刺激的预期，但仍然不清楚有害信息如何 进入ACC。在DP 2家长奖中，我们目前正在探索来自杏仁核的伤害性输入， 然而，疼痛相关信息还有其他关键的连接途径进入前扣带回，如中线 丘脑（MTh）。在这里，我们扩展了DP 2的研究，以研究莫尔+ MTh投射电路， 支配伤害感受性ACC区域。在目标1中，我们将确定阿片样物质伤害性感受的神经解剖学 神经电路使用活性依赖性病毒和小鼠遗传学，在目标2中，我们将确定功能性 利用细胞类型特异性操作和机器， 基于视觉的行为量化方法，这是在父母DP 2实验。完成 建议的研究将促进受训者的技术掌握几个先进的神经科学 技术，数据分析和统计，以及几个培训目标，以准备受训者的职业生涯， 疼痛神经生物学研究。