Neuropathic vs. inflammatory pain in chronic pancreatitis: can unique biomarkers be identified to guide mechanistic approaches to pain treatment?

慢性胰腺炎的神经性疼痛与炎性疼痛：是否可以确定独特的生物标志物来指导疼痛治疗的机制方法？

• 批准号: 10083736
• 负责人: Jami Lynn Saloman
• 金额: $ 14.92万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10083736
• 关键词: Abdomen; Abdominal Pain; Affect; Amylases; Analgesics; Animal Model; Animals; Behavior; Biological Assay; Biological Markers; Brain-Derived Neurotrophic Factor; Cells; Characteristics; Chronic; Clinic; Clinical; Clinical Research; Data; Development; Diagnosis; Etiology; Foundations; Functional disorder; Future; Glucose; Goals; Histology; Human; Immune; Inflammation; Inflammatory; Interleukin-1 beta; Knowledge; Lesion; Link; Lipase; Maps; Measures; Messenger RNA; Modeling; Molecular Target; Morphology; Nerve Growth Factors; Neurogenic Inflammation; Neuropathy; Neuropeptides; Nociception; Non-Steroidal Anti-Inflammatory Agents; Opioid; Pain; Pain management; Pancreas; Pancreatitis; Patient Monitoring; Patients; Pattern; Peripheral; Peroxidases; Pharmaceutical Preparations; Phenotype; Quality of life; Regimen; Sampling; Serum; Serum Proteins; Severities; Surveys; Symptoms; Testing; Therapeutic; Training; animal model development; animal pain; behavioral response; biomarker signature; chronic pancreatitis; cohort; conditioned place preference; cytokine; design; diagnosis design; experience; human data; inflammatory marker; inflammatory neuropathic pain; inflammatory pain; mouse model; nerve injury; new technology; novel; optogenetics; pain signal; pain symptom; painful neuropathy; patient biomarkers; prospective; recruit; relating to nervous system; therapeutic evaluation; tool; tool development

Abstract Chronic pancreatitis (CP) is often accompanied by profoundly debilitating pain that is quite difficult to treat. There are no tools available in clinics to properly characterize the subtype of pain a patient is experiencing to choose a therapy most likely to benefit a patient’s pain symptoms. There are two peripheral mechanisms that could contribute, inflammatory pain (IP) and neuropathic pain (NP). A major driver of IP is neurogenic inflammation, inflammation resulting from increased neural activity that drives release of neuropeptides that recruit/activate immune cells. NP results from direct nerve injury (compression or lesion). Importantly, both types of pain are accompanied by unique changes in cytokine expression that can be used to identify mechanisms (IP and/or NP) contributing to a patient’s pain. The development of tools to differentiate IP and NP in the clinic could ultimately streamline CP pain management because there is evidence that certain therapies are far more efficacious for one type of pain versus the other. For example, opioids are more effective for IP while gabapentinoids are more useful for NP. This proposal is designed to compare a novel animal model in which pancreatitis pain is induced purely by IP (optogenetic) and a commonly used animal model of CP (chronic cerulein) in which pain is a result of both IP and NP. The goal is to identify cytokine profiles associated with the specific pain phenotypes and compare to legacy samples from a well-characterized clinical cohort of CP patients. We will also test whether patients show correlations between cytokine profiles and pain characteristics. The long-term plan is to use an iterative approach that uses patient data to refine animal models of CP that can then be used to develop pain-type specific therapies. In addition to incorporating new technologies (optogenetic) to the study of CP, this project will provide in depth training in handling and analyzing human data and will provide a foundation for future prospective human studies that will include survey tools specifically designed for diagnosis of inflammatory and neuropathic pain in humans with CP.

抽象的 慢性胰腺炎（CP）通常伴随着令人衰弱的疼痛，这很难治疗。 诊所中没有任何工具可以正确地表征患者正在经历的疼痛亚型 选择最有可能使患者疼痛症状受益的疗法。有两种外围机制 可能会导致炎症性疼痛（IP）和神经性疼痛（NP）。 IP的主要驱动力是神经源 炎症，神经元活性增加引起的炎症，驱动神经肽的释放 募集/激活免疫细胞。 NP由直接神经损伤（压缩或病变）引起。重要的是，两者俩 疼痛的类型是通过可用于识别的细胞因子表达的独特变化来完成的 机制（IP和/或NP）导致患者的疼痛。开发区分IP和NP的工具 在诊所中最终可以简化CP疼痛管理，因为有证据表明某些疗法 对于一种类型的疼痛而言，比另一种疼痛更有效。例如，阿片类药物对IP更有效 而gabapentinoids对于NP更有用。该建议旨在比较一种新型动物模型 哪些胰腺炎疼痛纯粹是由IP（光遗传学）和CP的常用动物模型诱导的 （慢性Cerulein）疼痛是IP和NP的结果。目的是识别相关的细胞因子特征 具有特定的疼痛表型，并与特征良好的临床队列的传统样本进行比较 CP患者。我们还将测试患者是否显示细胞因子特征和疼痛之间的相关性 特征。长期计划是使用一种使用患者数据来完善动物的迭代方法 然后可以使用CP模型来开发疼痛类型的特定疗法。 除了将新技术（光遗传学）纳入CP研究外，该项目还将深入 处理和分析人类数据的培训，并将为未来的潜在人类提供基础 研究将包括专门设计用于炎症和神经性疼痛诊断的调查工具 人类与CP。