NOCICEPTOR AXONS AND NEURAL INFLAMMATION

描述（申请人摘要）：神经性疼痛可由神经 损伤或许多疾病过程，并且在没有轴突损伤的情况下发生。症状 通常难以在临床上控制，包括神经干疼痛， 在神经局部感知，以及在神经的 远端分布疼痛症状可以是自发的，也可以是 许多感觉迟钝疼痛的病例通过受影响神经的运动再现， 或其周围的组织。机械诱发的感觉障碍的观察 疼痛意味着轴突具有或获得了一种传导机制， 病理 拟议的实验解决了这样一个假设，即感觉迟钝疼痛导致 由于神经炎症引起的伤害感受器轴突的敏感性变化 携带轴突的细胞将从背根进行单单位记录 C-纤维与后肢的伤害感受野。坐骨神经 将在大腿中部被识别，远离感受野。内源 镇痛化学物质、炎症介质和促炎剂将被 应用于神经。神经元的性质，包括机械性质， 轴突的敏感性，将在之前和之后的不同时间进行测试 应用程序.在其他实验中，将诱导慢性神经炎， 神经元进行了类似的测试。 这些实验验证了神经炎症会导致 神经元功能的变化。此外，对所提问题的答复 将解决运动引起疼痛产生的新假设的一部分。 神经性疼痛的描述类似于一些神经性疼痛的特征。 慢性肌肉骨骼疼痛的形式，如肌筋膜疼痛综合征， 纤维肌痛和背痛对这些疾病的研究集中在 各种躯体组织作为疼痛源，但病因仍然难以捉摸， 因此，这种疾病的治疗方法不同。这些疾病可能 被误诊为神经病现有数据表明，局灶性神经病变是 一些慢性肌肉骨骼疾病，特别是背部 疼痛，通常会因运动而恶化。的信息 建议的研究所提供的将有助于形成发展的基础， 慢性运动诱发的肌肉骨骼疼痛的动物模型。

DESCRIPTION (APPLICANT'S ABSTRACT): Neuropathic pain can result from nerve injury or numerous disease processes, and occur without axonal injury. Symptoms are typically difficult to manage clinically, and include nerve trunk pain, perceived locally at the nerve, and dysesthetic pain, perceived in the nerve's distal distribution. Painful symptoms can be spontaneous, and can also be reproduced by many cases of dysesthetic pain by movement of the affected nerve, or the tissue surrounding it. Observations of mechanically-evoked dysesthetic pain imply that axons have or acquire a transductive mechanism at the site of pathology. The proposed experiments address the hypothesis that dysesthetic pain results from sensitivity changes of nociceptor axons due to inflammation of the nerve that carries its axon. Single-unit recording will be made from dorsal root C-fibers with a nociceptive receptive field in the hind limb. The sciatic nerve will be identified in mid thigh, remote from the receptive field. Endogenous algesic chemicals, inflammatory mediators, and pro-inflammatory agents will be applied to the nerve. The properties of the neuron, including the mechanical sensitivity of the axon, will be tested before and at various times following application. In other experiments, a chronic neuritis will be induced and the neurons similarly tested. These experiments test the hypothesis that inflammation of a nerve induces changes in neuronal function. Additional, the answers to the posed questions will address part of a novel hypothesis of movement-induced pain generation. Descriptions of neuropathic pain are similar to those characteristics of some forms of chronic musculoskeletal pain, such as myofascial pain syndrome, fibromyalgia, and back pain. Research into these disorders has focused on various somatic tissues as a pain source, but the etiologies remain elusive and thus the disorder are different to treat. It is possible that these disorders are misdiagnosed neuropathy. Existing data suggest that focal neuropathies are the root pathology in some chronic musculoskeletal diseases, especially back pain, that typically are symptomatically worsened by movement. The information provided by the proposed studies will help form a foundation for development of an animal model of chronic, movement-induced musculoskeletal pain.