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

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/7760594
• 关键词: Acute; Affect; Afferent Neurons; Affinity; Allergic; Ambrosia; Animals; Antigen-Antibody Complex; Antigens; Autoimmune Process; Behavior; Cells; Communicable Diseases; Control Animal; Cutaneous; Data; Development; Disease; Electrophysiology (science); Exhibits; Exploratory/Developmental Grant; Fc Receptor; Future; Hyperalgesia; IgG Receptors; Immune; Immune response; Immunoglobulin G; Immunohistochemistry; In Vitro; Inflammation; Location; Measures; Methods; Monitor; Nerve Tissue; Neurons; Nociception; Pain; Peripheral; Phase; Physiological; Pollen; Property; Rattus; Role; Sensory; Sensory Ganglia; Serum; Skin; Spinal Ganglia; Stimulus; Time; Tissues; Topical application; Up-Regulation; behavior test; chronic pain; immunoreactivity; in vivo; neurochemistry; neuronal cell body; neuronal excitability; novel; novel therapeutics; public health relevance; response

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（由申请方提供）：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（Fc 3RI）对初级感觉传入的兴奋作用。慢性疼痛常伴随自身免疫性、过敏性或感染性疾病，涉及外周组织、神经或感觉神经节中的抗原特异性免疫应答，但其潜在机制在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水平升高和受影响组织中IgG免疫复合物的存在。最近发现，背根神经节神经元的伤害性特性的亚群表达的高亲和力的IgG受体，Fc 3RI，并可以直接激活的IgG免疫复合物。初步数据表明，在先前免疫的大鼠中，用抗原激发的皮肤中的皮肤痛觉过敏比急性炎症的体征持续时间长。我建议探索特定的外来抗原，应用于皮肤或脊神经节，在免疫与未免疫的大鼠，对功能鉴定的伤害性初级感觉神经元的兴奋性和神经化学性质的影响，与Fc 3RI和疼痛相关的行为。本研究将通过IgG免疫复合物对初级感觉神经元表达的Fc受体的影响，揭示抗原特异性免疫应答驱动的慢性疼痛的新机制。它将为慢性疼痛的治疗提供潜在的新的治疗策略。公共卫生相关性：本研究将通过IgG免疫复合物对初级感觉神经元表达的Fc受体的影响，揭示抗原特异性免疫应答驱动的慢性疼痛的新机制。它将为慢性疼痛的治疗提供潜在的新的治疗策略。

项目成果

Neuronal Fc-gamma receptor I mediated excitatory effects of IgG immune complex on rat dorsal root ganglion neurons.

• DOI: 10.1016/j.bbi.2011.04.008
• 发表时间: 2011-10
• 期刊: BRAIN BEHAVIOR AND IMMUNITY
• 影响因子: 15.1
• 作者: Qu, Lintao;Zhang, Pu;LaMotte, Robert H.;Ma, Chao
• 通讯作者: Ma, Chao

Transient receptor potential canonical 3 (TRPC3) is required for IgG immune complex-induced excitation of the rat dorsal root ganglion neurons.

• DOI: 10.1523/jneurosci.6355-11.2012
• 发表时间: 2012-07-11
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Qu L;Li Y;Pan X;Zhang P;LaMotte RH;Ma C
• 通讯作者: Ma C