Antigen-specific immune mechanisms of neuronal hyperexcitability and chronic pain

神经元过度兴奋和慢性疼痛的抗原特异性免疫机制

基本信息

批准号：
7760594
负责人：
Chao Ma
金额：
$ 21.5万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-02-01 至 2011-07-31
项目状态：
已结题

项目摘要

Description (provided by applicant): A novel mechanism of chronic pain will be explored: the excitatory effects of the immunoglobulin G (IgG) immune complex on primary sensory afferents via neuronal Fc gamma receptor I (Fc3RI). Chronic pain often accompanies autoimmune, allergic or infectious diseases involving antigen-specific immune responses in the peripheral tissue, nerve or sensory ganglia though the underlying mechanisms are largely unknown. A common feature among these disorders is the elevated level of antigen-specific IgG in the serum and the presence of IgG immune complex in the affected tissue. Recently it was discovered that a subpopulation of dorsal root ganglion neurons with nociceptive properties expressed the high-affinity IgG receptor, Fc3RI and could be directly activated by IgG immune complex. Preliminary data indicate that cutaneous hyperalgesia in skin challenged with antigen in previously immunized rats long outlasts signs of acute inflammation. I propose to explore the effects of a specific foreign antigen, applied to the skin or to the spinal ganglia, in immunized vs. unimmunized rats, on the excitability and neurochemical properties of functionally identified nociceptive primary sensory neurons in relation to Fc3RI and pain-related behaviors. This study will reveal a novel mechanism of chronic pain driven by the antigen-specific immune response via the effects of IgG immune complex on the Fc receptors expressed in primary sensory neurons. It will provide potentially new therapeutic strategies in the treatment of chronic pain. PUBLIC HEALTH RELEVANCE: This study will reveal a novel mechanism of chronic pain driven by the antigen-specific immune response via the effects of IgG immune complex on the Fc receptors expressed in primary sensory neurons. It will provide potentially new therapeutic strategies in the treatment of chronic pain.

描述（由申请人提供）：将探索慢性疼痛的新机制：免疫球蛋白 G (IgG) 免疫复合物通过神经元 Fc γ 受体 I (Fc3RI) 对初级感觉传入的兴奋作用。慢性疼痛通常伴随自身免疫性疾病、过敏性疾病或感染性疾病，涉及周围组织、神经或感觉神经节中的抗原特异性免疫反应，但其潜在机制很大程度上尚不清楚。这些疾病的一个共同特征是血清中抗原特异性 IgG 水平升高以及受影响组织中存在 IgG 免疫复合物。最近发现，具有伤害感受特性的背根神经节神经元亚群表达高亲和力 IgG 受体 Fc3RI，并且可以直接被 IgG 免疫复合物激活。初步数据表明，在先前免疫的大鼠中，受到抗原刺激的皮肤中的皮肤痛觉过敏比急性炎症的症状持续得更久。我建议在免疫大鼠与未免疫大鼠中探索应用于皮肤或脊神经节的特定外来抗原对功能上识别的伤害性初级感觉神经元的兴奋性和神经化学特性的影响，这些神经元与 Fc3RI 和疼痛相关行为。这项研究将通过 IgG 免疫复合物对初级感觉神经元表达的 Fc 受体的影响，揭示由抗原特异性免疫反应驱动的慢性疼痛的新机制。它将为治疗慢性疼痛提供潜在的新治疗策略。公共健康相关性：这项研究将揭示一种慢性疼痛的新机制，该机制是由抗原特异性免疫反应通过 IgG 免疫复合物对初级感觉神经元表达的 Fc 受体的影响而驱动的。它将为治疗慢性疼痛提供潜在的新治疗策略。