Neurogeneic Amplification of Pancreatitis Pain

胰腺炎疼痛的神经源性放大

• 批准号: 7871859
• 负责人: KARIN N. WESTLUND-HIGH
• 金额: $ 5.6万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7871859
• 关键词: Abdominal Pain; Animals; Behavioral; Blood; Blood Volume; Brain; Cell Nucleus; Cells; Central cord canal structure; Characteristics; Chest; Chronic; Clinical; Clinical Treatment; Communities; Dorsal; Endothelin; Follow-Up Studies; Functional Magnetic Resonance Imaging; Future; Goals; Histology; Human; Inbred Lew Rats; Laboratories; Lead; Lesion; Malignant Neoplasms; Malignant neoplasm of pancreas; Medial; Medical; Methods; Modeling; Morphine; Neurons; Nociception; Operative Surgical Procedures; Organ; Outcome; Pain; Pan Genus; Pancreas; Pancreatitis; Pathway interactions; Patients; Pelvic Cancer; Pelvis; Persistent pain; Physiological; Play; Pontine structure; Process; Psyche structure; Rattus; Refractory; Reporting; Research Personnel; Resistance; Role; Route; Sensory; Sensory Process; Signal Transduction; Spinal; Spinal Cord; Structure; Sympathetic Nerve Block; Syndrome; System; Thalamic structure; Visceral; Visceral Afferents; Visceral pain; cancer pain; central sensitization; clinically relevant; dorsal column; imaging modality; improved; insight; interdisciplinary approach; midbrain central gray substance; novel; postsynaptic; programs; raphe nuclei; research study; response; therapeutic target; transmission process

DESCRIPTION (provided by applicant): Many patients with pancreatitis or pancreatic cancer complain of abdominal pain that is resistant even to morphine. Our previous studies have determined that pain in patients with cancer involving the pelvic visceral organs is relieved by a neurosurgical lesion limited to the midline of the dorsal column of the spinal cord. We determined that sensory input from the pancreas is primarily transmitted to higher brain sensory processing centers as a midline component of the postsynaptic dorsal column pathway using anatomical, electrophysiological and behavioral methods. In our laboratory recently we have developed a model of persistent visceral pain in Lewis inbred rats that resembles human pancreatitis in blood values and histology. The purpose of the proposed project is to study the neuronal pathway by which pain signals from the pancreas reach higher brain centers and how sensitization of this pathway can lead to persistent pain states. A multidisciplinary approach is used including behavioral, electrophysiological, and functional magnetic resonance imaging (fMRI) methods. The following hypothesis and specific aims were devised to improve our understanding of chronic visceral pain processing toward the long term goal of improved therapy: HYPOTHESIS: Nociceptive information arising from the inflamed pancreas is relayed in the spinal cord, transmitted through medially ascending pathways to higher centers, and produces central sensitization in medially located brain structures. Specific Aim 1 is to determine the nociceptive pathways activated in persistent pancreatitis. Specific Aim 2 is to reduce activation in the visceral nociceptive pathways maintaining central sensitization in a persistent pancreatitis model in Lewis inbred rats. The long-term outcome expected is that information about the visceral nociceptive pathway will contribute to future identification of therapeutic targets for these devastatingly painful conditions involving the pancreas.

描述（由申请人提供）：许多胰腺炎或胰腺癌患者抱怨腹痛甚至对吗啡产生耐药性。我们之前的研究已经确定，涉及盆腔内脏器官的癌症患者的疼痛可以通过仅限于脊髓背柱中线的神经外科病变来缓解。我们使用解剖学、电生理学和行为方法确定，来自胰腺的感觉输入主要传输到高级大脑感觉处理中心，作为突触后背柱通路的中线组成部分。最近，我们的实验室在路易斯近交系大鼠中开发了一种持续性内脏疼痛模型，其血液值和组织学类似于人类胰腺炎。该项目的目的是研究来自胰腺的疼痛信号到达高级大脑中心的神经元通路，以及该通路的敏化如何导致持续性疼痛状态。采用多学科方法，包括行为学、电生理学和功能磁共振成像 (fMRI) 方法。 设计以下假设和具体目标是为了提高我们对慢性内脏疼痛处理的理解，以实现改善治疗的长期目标： 假设：发炎的胰腺产生的伤害性信息在脊髓中传递，通过内侧上升路径传递到更高的中枢，并在位于内侧的大脑结构中产生中枢敏化。 具体目标 1 是确定持续性胰腺炎中激活的伤害感受通路。具体目标 2 是减少内脏伤害性通路的激活，维持 Lewis 近交系大鼠持续性胰腺炎模型中的中枢敏化。 预期的长期结果是，有关内脏伤害性通路的信息将有助于未来确定这些涉及胰腺的毁灭性疼痛病症的治疗靶点。