Changes in blood-spinal cord barrier permeability and neuroimmune interactions in the underlying mechanisms of chronic pain.
Changes in blood-spinal cord barrier permeability and neuroimmune interactions in the underlying mechanisms of chronic pain.
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DOI：
10.1097/pr9.0000000000000879
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发表时间：
2021
期刊：
影响因子：
4.8
通讯作者：
Malcangio M
中科院分区：
文献类型：
--
作者：
Montague-Cardoso K;Malcangio M
在这里，我们讨论血脊髓屏障通透性改变的证据，并考虑慢性疼痛模型中相关神经免疫通讯改变的可能性。推进我们对慢性疼痛的潜在机制的理解有助于确定新的潜在治疗靶点。贯穿疼痛通路的神经免疫通讯具有至关重要的机制重要性，并且在过去20年中一直是临床前慢性疼痛研究的主要焦点。在脊髓中，背角神经元不仅与常驻免疫细胞（如小胶质细胞）进行机械上重要的双向交流，而且在某些情况下，它们还可以与免疫细胞（如从循环中浸润到脊髓中的单核细胞/巨噬细胞）进行双向串扰。免疫细胞向脊髓的浸润可以部分地通过血脊髓屏障（BSCB）渗透性的变化来调节。在这里，我们讨论了支持和反对临床前慢性疼痛中BSCB破坏和神经免疫串扰相关变化的机制作用的证据。我们也考虑到最近的证据表明它可能参与化疗引起的疼痛性神经病变的长春新碱模型。我们的结论是，目前的知识需要进一步研究，以确定预防BSCB破坏，或针对与这种破坏相关的变化，是否可以用于开发治疗慢性疼痛的新方法。
Here, we discuss evidence for changes in blood–spinal cord barrier permeability and consider the possibility of associated neuroimmune communication changes in models of chronic pain. Advancing our understanding of the underlying mechanisms of chronic pain is instrumental to the identification of new potential therapeutic targets. Neuroimmune communication throughout the pain pathway is of crucial mechanistic importance and has been a major focus of preclinical chronic pain research over the last 2 decades. In the spinal cord, not only do dorsal horn neurons partake in mechanistically important bidirectional communication with resident immune cells such as microglia, but in some cases, they can also partake in bidirectional crosstalk with immune cells, such as monocytes/macrophages, which have infiltrated into the spinal cord from the circulation. The infiltration of immune cells into the spinal cord can be partly regulated by changes in permeability of the blood–spinal cord barrier (BSCB). Here, we discuss evidence for and against a mechanistic role for BSCB disruption and associated changes in neuroimmune crosstalk in preclinical chronic pain. We also consider recent evidence for its potential involvement in the vincristine model of chemotherapy-induced painful neuropathy. We conclude that current knowledge warrants further investigation to establish whether preventing BSCB disruption, or targeting the changes associated with this disruption, could be used for the development of novel approaches to treating chronic pain.