Neuroinflammation, Bone Marrow Stem Cells, and Chronic Pain.
Neuroinflammation, Bone Marrow Stem Cells, and Chronic Pain.
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神经炎症，骨髓干细胞和慢性疼痛。
DOI：
10.3389/fimmu.2017.01014
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发表时间：
2017
影响因子：
7.3
通讯作者：
Chen G
中科院分区：
文献类型：
--
作者：
Huh Y;Ji RR;Chen G
目前对慢性疼痛的治疗，如炎症性疼痛、神经病理性疼痛和癌症疼痛，都是不够的，并会产生严重的副作用。越来越多的证据表明，周围和中枢神经系统(PNS和CNS)的神经炎症在慢性疼痛的发生和维持中起着关键作用。慢性疼痛条件下神经炎症的特征包括免疫细胞渗入三叉神经节[如坐骨神经和背根神经节]，中枢神经系统(脊髓和脑)的小胶质细胞和星形胶质细胞等胶质细胞激活，促炎细胞因子和趋化因子[肿瘤坏死因子、白介素1β、白介素6、CCL2和CXCL1]的产生和分泌。最近的研究表明，骨髓干细胞或骨髓基质细胞(BMSCs)在炎症性疼痛、神经病理性疼痛和癌症疼痛的动物模型中具有强大的镇痛作用。我们最近证实，鞘内注射骨髓间充质干细胞可以长期缓解周围神经损伤后数周的神经病理性疼痛。值得注意的是，这种止痛作用是由骨髓间充质干细胞分泌的抗炎细胞因子转化生长因子β介导的。此外，骨髓间充质干细胞通过抑制背根神经节和脊髓中单核细胞的渗透、胶质细胞的激活以及细胞因子/趋化因子的产生，对神经炎症有很强的调节作用。因此，BMSCs通过旁分泌信号调节三叉神经节和中枢神经系统的神经炎症，从而控制慢性疼痛。在这篇综述中，我们讨论了不同实验室在动物和临床研究中发现的具有显著抗伤害效应的BMSCs相似的结果。我们还讨论了骨髓间充质干细胞控制神经炎症和慢性疼痛的机制，以及这些细胞如何特异性地迁移到受损组织。
Current treatments for chronic pain, such as inflammatory pain, neuropathic pain, and cancer pain are insufficient and cause severe side effects. Mounting evidence suggests that neuroinflammation in the peripheral and central nervous system (PNS and CNS) plays a pivotal role in the genesis and maintenance of chronic pain. Characteristic features of neuroinflammation in chronic pain conditions include infiltration of immune cells into the PNS [e.g., the sciatic nerve and dorsal root ganglion (DRG)], activation of glial cells such as microglia and astrocytes in the CNS (spinal cord and brain), and production and secretion of pro-inflammatory cytokines and chemokines [TNF, interleukin (IL)-1β, IL-6, CCL2, and CXCL1]. Recent studies suggest that bone marrow stem cells or bone marrow stromal cells (BMSCs) produce powerful analgesic effects in animal models of inflammatory pain, neuropathic pain, and cancer pain. We recently demonstrated that intrathecal injection of BMSCs resulted in a long-term relief of neuropathic pain for several weeks after peripheral nerve injury. Strikingly, this analgesic effect is mediated by the anti-inflammatory cytokine transforming growth factor beta secreted from BMSCs. Additionally, BMSCs exhibit potent modulation of neuroinflammation, by inhibiting monocyte infiltration, glial activation, and cytokine/chemokine production in the DRG and spinal cord. Thus, BMSCs control chronic pain by regulation of neuroinflammation in the PNS and CNS via paracrine signaling. In this review, we discuss the similar results from different laboratories of remarkable anti-nociceptive efficacy of BMSCs in animal and clinical studies. We also discuss the mechanisms by which BMSCs control neuroinflammation and chronic pain and how these cells specifically migrate to damaged tissues.
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