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

这些研究旨在验证以下假设，即背角神经元对来自下背部肌肉和胸腰椎筋膜的输入的敏化是非特异性慢性下背部疼痛发展的关键因素，并且取决于两个主要机制：1.增加来自外周伤害感受器的传入输入。通常，伤害性输入发生时患者未注意到，但它可能导致脊髓背角神经元的潜在敏化。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。该假设将在三种下背痛动物模型中进行测试：即1.多裂肌或胸腰椎筋膜的炎症，2.通过重复注射神经生长因子（NGF）引起的非炎性伤害性输入，和3.由于固定而产生的压力。这些方法包括背角神经元的电生理在体记录与行为实验相结合。这种结合很重要，因为初步数据表明，中枢致敏可以在没有任何行为变化的情况下发生。此外;通过长期鞘内给药，将测试神经胶质细胞和神经元之间的脊髓信号传导途径在潜在致敏中的相关性。 本研究的目的是：1.在我们的3种LBP模型（系列1和系列2）中，发现神经元、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了腰背角神经元的敏化。与此相关的是，我们希望获得有关神经元潜在敏化的物质的新见解。 2.观察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诱导的脊髓敏化。 3.观察胸腰段筋膜中的外周伤害感受和交感神经末梢是否存在炎症诱导的变化（例如分支模式、静脉曲张数量）。在与目标1和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。最终目的是生成无法在患者中获得的非特异性下背痛的机制数据，并找出3种下背痛模型与不同下背痛患者组（例如病变诱导的，压力诱导的）之间是否存在相似之处。

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.