Interventions to prevent and reverse chronic spinal sensitization in rat models of non-specific low back pain.

在非特异性腰痛大鼠模型中预防和逆转慢性脊柱敏化的干预措施。

• 批准号: 317559845
• 负责人: Professor Dr. Siegfried Mense
• 金额: --
• 依托单位: Lehrstuhl Neuroanatomie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/317559845?language=en
• 关键词: Interventions; prevent; reverse; chronic; spinal

The studies are designed to test the hypothesis that sensitization of dorsal horn neurons with input from low back muscles and thoracolumbar fascia is a key factor for the development of non-specific chronic low back pain and depends on two main mechanisms: 1. Increased afferent input from peripheral nociceptors. Often, the nociceptive input occurs unnoticed by the patient, but it may cause a latent sensitization of spinal dorsal horn neurons. 2. Dysfunction of the descending pain-modulating systems. In this mechanism, stress plays an important role. The hypothesis will be tested in three animal models of low back pain: namely 1. inflammation of the multifidus muscle or thoracolumbar fascia, 2. non-inflammatory nociceptive input elicited by repeated injections of nerve growth factor (NGF), and 3. stress due to immobilization. The methods include electrophysiological in vivo recordings from dorsal horn neurons combined with behavioral experiments. This combination is important, because preliminary data show that central sensitization can occur without any behavioral changes. Further; by chronic intrathecal drug administration the relevance of spinal signaling pathways between glial cells and neurons in the latent sensitization will be tested. The aims of the study are: 1. To find out to what extent spinal signaling pathways between neurons, microglia and astrocytes, are involved in the sensitization of lumbar dorsal horn neurons in our 3 models of LBP (series 1 and 2). In connection with this aim, we hope to gain new insights into the substances that are involved in the latent sensitization of the neurons. 2. To see if and how blocking the descending pain-modulating systems or the sympathetic system influence the nociceptive and stress-induced spinal sensitization. 3. To see if there are inflammation-induced changes (e.g. branching patterns, number of varicosities) in peripheral nociceptive and sympathetic nerve endings in the thoracolumbar fascia. In the experiments connected to aims 1 and 2, treatments will be tested that have the potential to prevent, attenuate or reverse the chronic sensitization. The final aim is to generate data on the mechanisms underlying non-specific low back pain that cannot be obtained in patients, and to find out if parallels between the 3 low back pain models and different groups of low back pain patients (e.g. lesion-induced, stress-induced) exist.

本研究旨在验证以下假设：来自腰背部肌肉和胸腰筋膜输入的背角神经元致敏是非特异性慢性腰痛发展的关键因素，并依赖于两个主要机制：1。外周伤害感受器传入输入增加。通常，患者未注意到伤害性输入，但它可能引起脊髓背角神经元的潜在致敏。2. 下行疼痛调节系统功能障碍。在这一机制中，压力起着重要作用。该假设将在三种腰痛动物模型中进行验证：1。多裂肌或胸腰筋膜炎症；2 .反复注射神经生长因子（NGF）引起的非炎性伤害性输入；由于固定造成的压力。方法包括背角神经元的体内电生理记录与行为实验相结合。这种组合很重要，因为初步数据表明中枢致敏可以在没有任何行为改变的情况下发生。进一步;通过慢性鞘内给药，将测试神经胶质细胞和神经元之间的脊髓信号通路在潜在致敏中的相关性。本研究的目的是：1。在我们的3种腰痛模型（系列1和系列2）中，探讨神经元、小胶质细胞和星形胶质细胞之间的脊髓信号通路在多大程度上参与腰背角神经元的致敏。为了达到这一目的，我们希望对参与神经元潜在敏化的物质有新的认识。2. 看看阻断下行疼痛调节系统或交感神经系统是否以及如何影响伤害性和应激性脊髓致敏。3. 观察胸腰筋膜外周痛觉神经末梢和交感神经末梢是否有炎症引起的改变（如分支模式、静脉曲张数）。在与目标1和目标2相关的实验中，将测试有可能预防、减弱或逆转慢性致敏的治疗方法。最终目的是获得无法在患者中获得的非特异性腰痛机制的数据，并找出3种腰痛模型和不同腰痛患者群体（如病变诱导、应激诱导）之间是否存在相似之处。