IMMUNE-MEDIATED INFLAMMATION IN DORSAL ROOT GANGLIA AFTER PERIPHERAL NERVE INJURY AND IN SENSORY NEUROPATHIES

神经系统的损伤可由意外或医源性创伤、毒素、感染、代谢紊乱甚至正常衰老引起。其后果可能超过伤害的直接影响。几乎所有对神经系统的损伤都会导致神经细胞的丧失，从而改变感觉和运动。神经损伤后还可能出现感觉障碍，从刺痛、麻木和异常温度感觉到自发疼痛、异常痛觉（轻触引起的疼痛感觉）或痛觉过敏（对破坏性刺激的敏感性增加）。其中一些症状出现在老年人身上，因为他们失去了感觉神经元。这些问题是慢性的，而且大多数对药物来说是难以治愈的。该项目将阐明免疫介导的背根（感觉）神经节（DRGs）炎症如何导致这些后遗症。即使是周围神经损伤后最简单形式的神经损伤，也会在远离损伤直接涉及部位的神经系统区域产生变化。我们最近的工作首次描述了免疫系统在大鼠远端周围神经横断后触发DRGs变化的参与。t细胞激活导致巨噬细胞的侵袭和促炎细胞因子的产生。这些物质可以激活感觉神经元，并可能导致进行性神经元死亡。因此，我们建立了一个简单的系统，我们可以评估不同种类的t细胞和巨噬细胞在损伤和其他损伤后流入DRGs。我们打算用它来定义参与免疫细胞募集的细胞事件序列，并将其与已知的在该系统中产生神经免疫反应的其他实验干预措施进行比较。这将确定DRG是否是神经免疫相互作用的特殊部位，因此应该作为治疗的靶点。

Damage to the nervous system can occur because of accidental or iatrogenic trauma, toxins, infection, metabolic disorders, and even normal ageing. The consequences can outweigh the direct effects of the injury. Almost all injury to the nervous system results in loss of nerve cells and consequently modified sensation and movement. Nerve damage may also be followed by sensory disturbances, ranging from tingling, numbness and abnormal temperature sensations to spontaneous pain, allodynia (painful sensations from light touch) or hyperalgesia (increased sensitivity to a damaging stimulus). Some of these symptoms are encountered in older people as they lose sensory neurones. The problems are chronic and most are intractable to drugs. This project will clarify how immune-mediated inflammation of dorsal root (sensory) ganglia (DRGs) contributes to these sequelae. Even the simplest form of neural damage following peripheral nerve injury can produce changes in regions of the nervous system far from the parts directly involved in the injury. Our recent work has described for the first time the involvement of the immune system in triggering changes in DRGs following transection of a distant peripheral nerve in rats. T-cell activation leads to invasion of macrophages and production of proinflammatory cytokines. These substances can activate sensory neurones and may be responsible for progressive neuronal death. Thus we have established a simple system in which we can evaluate the influx of T-cells and macrophages of different kinds into DRGs after injury and other insults. We intend to use this to define the sequence of cellular events involved in recruitment of immune cells and compare it with other experimental interventions known to produce a neuroimmune response in this system. This will identify whether the DRG is a special site for neuroimmune interactions and so should be a target for therapy.