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: 10335169
• 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/10335169
• 关键词: 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; Technology; Testing; Therapeutic; Training; animal model development; animal pain; behavioral response; biomarker signature; chronic pancreatitis; cohort; conditioned place preference; cytokine; debilitating pain; 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）通常伴有严重的令人衰弱的疼痛，而且很难治疗。 临床上没有可用的工具来正确描述患者正在经历的疼痛亚型 选择最有可能缓解患者疼痛症状的疗法。有两个外围机制 可能会导致炎症性疼痛（IP）和神经性疼痛（NP）。知识产权的主要驱动力是神经源性的 炎症，由于神经活动增加而导致的炎症，神经活动增加会驱动神经肽的释放， 招募/激活免疫细胞。 NP 由直接神经损伤（压迫或损伤）引起。重要的是，两者 疼痛类型伴随着细胞因子表达的独特变化，可用于识别 导致患者疼痛的机制（IP 和/或 NP）。开发区分IP和NP的工具 临床上的应用最终可以简化脑瘫疼痛管理，因为有证据表明某些疗法 对于一种类型的疼痛比另一种类型的疼痛更有效。例如，阿片类药物对于 IP 更有效 而加巴喷丁类药物对于 NP 更有用。该提案旨在比较一种新颖的动物模型 胰腺炎疼痛纯粹由IP（光遗传学）诱导，是一种常用的CP动物模型 （慢性雨蛙素），其中疼痛是 IP 和 NP 共同造成的。目标是确定相关的细胞因子谱 具有特定的疼痛表型，并与来自充分表征的临床队列的遗留样本进行比较 脑瘫患者。我们还将测试患者是否表现出细胞因子谱与疼痛之间的相关性 特征。长期计划是使用迭代方法，利用患者数据来完善动物 CP 模型可用于开发疼痛类型的特异性疗法。 除了将新技术（光遗传学）纳入 CP 研究之外，该项目还将提供深入的研究 处理和分析人类数据的培训将为未来的未来人类奠定基础 研究将包括专门为诊断炎症和神经性疼痛而设计的调查工具 有CP的人类。