The immune system has long been recognised important in pain regulation through inflammatory cytokine modulation of peripheral nociceptive fibres. Recently, cytokine interactions in brain and spinal cord glia as well as dorsal root ganglia satellite glia have been identified important- in pain modulation. The result of these interactions is central and peripheral sensitisation of nociceptive processing. Additionally, new insights and the term 'autoimmune pain' have emerged through discovery of specific IgGs targeting the extracellular domains of antigens at nodal and synaptic structures, causing pain directly without inflammation by enhancing neuronal excitability. Other discovered IgGs heighten pain indirectly by T-cell-mediated inflammation or destruction of targets within the nociceptive pathways. Notable identified IgGs in pain include those against the components of channels and receptors involved in inhibitory or excitatory somatosensory synapses or their pathways: nodal and paranodal proteins (LGI1, CASPR1, CASPR2); glutamate detection (AMPA-R); GABA regulation and release (GAD65, amphiphysin); glycine receptors (GLY-R); water channels (AQP4). These disorders have other neurological manifestations of central/peripheral hyperexcitabability including seizures, encephalopathy, myoclonus, tremor and spasticity, with immunotherapy responsiveness. Other pain disorders, like complex regional pain disorder, have been associated with IgGs against β2-adrenergic receptor, muscarinic-2 receptors, AChR-nicotinic ganglionic α-3 receptors and calcium channels (N and P/Q types), but less consistently with immune treatment response. Here, we outline how the immune system contributes to development and regulation of pain, review specific IgG-mediated pain disorders and summarise recent development in therapy approaches. Biological agents to treat pain (anti-calcitonin gene-related peptide and anti-nerve growth factor) are also discussed.

中文翻译：

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疼痛和免疫系统：IgG 介导的自身免疫性疼痛和免疫疗法的新兴概念。

长期以来，人们一直认为免疫系统通过外周伤害感受纤维的炎症细胞因子调节在疼痛调节中很重要。最近，已确定脑和脊髓神经胶质细胞以及背根神经节卫星神经胶质细胞中的细胞因子相互作用在疼痛调节中很重要。这些相互作用的结果是伤害感受处理的中枢和外周敏化。此外，新的见解和术语“自身免疫性疼痛”是通过发现靶向淋巴结和突触结构处抗原的细胞外结构域的特异性 IgG 产生的，通过增强神经元的兴奋性直接引起疼痛而不发炎。其他发现的 IgG 通过 T 细胞介导的炎症或伤害感受通路内靶点的破坏间接加重疼痛。疼痛中值得注意的 IgG 包括那些针对参与抑制性或兴奋性体感突触或其通路的通道和受体成分的 IgG：结节和结节旁蛋白（LGI1、CASPR1、CASPR2）；谷氨酸检测（AMPA-R）；GABA 调节和释放（GAD65，amphiphysin）；甘氨酸受体（GLY-R）；水道 (AQP4)。这些疾病具有其他中枢/外周过度兴奋的神经系统表现，包括癫痫发作、脑病、肌阵挛、震颤和痉挛，具有免疫治疗反应性。其他疼痛障碍，如复杂性局部疼痛障碍，与针对 β2-肾上腺素能受体、毒蕈碱 2 受体、AChR-烟碱神经节 α-3 受体和钙通道（N 和 P/Q 型）的 IgG 相关，但与免疫治疗反应。这里，我们概述了免疫系统如何促进疼痛的发展和调节，回顾了特定的 IgG 介导的疼痛疾病，并总结了治疗方法的最新发展。还讨论了治疗疼痛的生物制剂（抗降钙素基因相关肽和抗神经生长因子）。