Mediators of Neuropathic Pain; Focus on Spinal Microglia, CSF-1, BDNF, CCL21, TNF-α, Wnt Ligands, and Interleukin 1β.
Mediators of Neuropathic Pain; Focus on Spinal Microglia, CSF-1, BDNF, CCL21, TNF-α, Wnt Ligands, and Interleukin 1β.
复制标题
DOI：
10.3389/fpain.2021.698157
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Smith PA
中科院分区：
文献类型：
--
作者：
Boakye PA;Tang SJ;Smith PA
顽固性神经性疼痛是神经损伤或疾病的常见后果。当周围神经受损时，受损的轴突发生沃勒氏变性。雪旺细胞、肥大细胞、成纤维细胞、角化细胞和上皮细胞被激活，导致产生含有细胞因子、趋化因子和生长因子的“炎症汤”。这些初级介质使感觉神经末梢敏感，吸引巨噬细胞、中性粒细胞和淋巴细胞，改变基因表达，促进蛋白质的翻译后修饰，并改变初级传入神经元的离子通道功能。这导致兴奋性和自发活性增加，并产生二级介质，包括集落刺激因子1 （CSF-1）、趋化因子C-C基序配体21 （CCL-21）、Wnt3a和Wnt5a。从初级传入神经元释放这些介质会改变脊髓小胶质细胞的特性，导致它们在许多情况下通过atp依赖机制释放三级介质。三级介质如BDNF、肿瘤坏死因子α (TNF-α)、白细胞介素1β (IL-1β)等Wnt配体通过增加脊髓背角兴奋性谷氨酸能传递和减弱抑制性GABA和甘氨酸能传递，促进伤害性信息的产生和传递。本文综述了二级介质对小胶质细胞的激活、三级介质对小胶质细胞的释放以及它们在脊髓背角中的作用。人们注意到，与女性相比，各种介质在男性中的确切作用存在实质性差异。至少有25种不同的介质已被确定，但它们在感觉神经末梢、背根神经节和脊髓中的作用的相似性意味着在可用的机制中存在相当多的冗余。尽管如此，行为学研究表明，中断任何单一介质的行为都可以减轻实验动物的疼痛迹象。我们提请注意这个悖论。很难解释当有这么多平行通路可用时，一个介质的失活如何能减轻疼痛。
Intractable neuropathic pain is a frequent consequence of nerve injury or disease. When peripheral nerves are injured, damaged axons undergo Wallerian degeneration. Schwann cells, mast cells, fibroblasts, keratinocytes and epithelial cells are activated leading to the generation of an “inflammatory soup” containing cytokines, chemokines and growth factors. These primary mediators sensitize sensory nerve endings, attract macrophages, neutrophils and lymphocytes, alter gene expression, promote post-translational modification of proteins, and alter ion channel function in primary afferent neurons. This leads to increased excitability and spontaneous activity and the generation of secondary mediators including colony stimulating factor 1 (CSF-1), chemokine C-C motif ligand 21 (CCL-21), Wnt3a, and Wnt5a. Release of these mediators from primary afferent neurons alters the properties of spinal microglial cells causing them to release tertiary mediators, in many situations via ATP-dependent mechanisms. Tertiary mediators such as BDNF, tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and other Wnt ligands facilitate the generation and transmission of nociceptive information by increasing excitatory glutamatergic transmission and attenuating inhibitory GABA and glycinergic transmission in the spinal dorsal horn. This review focusses on activation of microglia by secondary mediators, release of tertiary mediators from microglia and a description of their actions in the spinal dorsal horn. Attention is drawn to the substantial differences in the precise roles of various mediators in males compared to females. At least 25 different mediators have been identified but the similarity of their actions at sensory nerve endings, in the dorsal root ganglia and in the spinal cord means there is considerable redundancy in the available mechanisms. Despite this, behavioral studies show that interruption of the actions of any single mediator can relieve signs of pain in experimental animals. We draw attention this paradox. It is difficult to explain how inactivation of one mediator can relieve pain when so many parallel pathways are available.
登录
查看更多内容
影响因子：
4.5
作者：
Andrade, Pablo;Cornips, Erwin M. J.;Hoogland, Govert
通讯作者：
Hoogland, Govert
影响因子：
3.6
作者：
Andrews, N.;Legg, E.;Rice, A. S. C.
通讯作者：
Rice, A. S. C.
影响因子：
3.5
作者：
Baba, H;Ji, RR;Woolf, CJ
通讯作者：
Woolf, CJ
背根神经节和脊髓中趋化因子 CXCL12 的上调有助于大鼠神经损伤后神经病理性疼痛的发生和维持
影响因子：
5.6
作者：
Bai, Liying;Wang, Xinru;Xu, Ji-Tian
通讯作者：
Xu, Ji-Tian
影响因子：
4.8
作者：
Acharjee, Shaona;Noorbakhsh, Farshid;Power, Christopher
通讯作者：
Power, Christopher