Modulation of Glia-Mediated Processes by Spinal Cord Stimulation in Animal Models of Neuropathic Pain.
Modulation of Glia-Mediated Processes by Spinal Cord Stimulation in Animal Models of Neuropathic Pain.
复制标题
DOI：
10.3389/fpain.2021.702906
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Vallejo R
中科院分区：
文献类型：
--
作者：
Cedeño DL;Kelley CA;Chakravarthy K;Vallejo R
神经胶质细胞在维持神经系统的正常功能方面发挥着重要作用。它们比大多数神经组织中的神经元更丰富，并提供代谢和分解代谢调节，维持突触的稳态平衡。慢性疼痛是通过中枢神经系统中胶质介导的过程被破坏而产生和持续的，导致神经元-胶质相互作用不平衡。神经病理性疼痛的动物模型已被用于证明在疼痛慢性化过程中发生免疫和神经炎症过程的变化。脊髓刺激（SCS）是一种经证实安全有效的神经电调节疗法，可用于治疗顽固性慢性疼痛。传统的SCS疗法是基于疼痛的门控理论开发的，并且依赖于刺激大的Aβ神经元来诱导疼痛皮区中的感觉异常，旨在掩盖由小感觉神经元进行的伤害性输入。SCS治疗引入了范式转变，无需感觉异常即可有效缓解疼痛。为了理解SCS的作用机制，已经考虑了神经胶质细胞的作用和电参数对神经元-神经胶质相互作用的影响。最近的工作提供了证据表明，SCS影响神经胶质相关基因和蛋白质的表达水平。这启发了使用电信号的差异靶多路复用编程（DTMP）方法的开发，该方法可以通过差异地靶向神经元和神经胶质细胞来重新平衡神经胶质相互作用。我们小组率先利用转录组学和蛋白质组学分析来确定SCS工作的作用机制，强调DTMP方法。这是一个使用神经病理性疼痛模型证明SCS对胶质介导过程的影响的证据说明，强调依赖于评估大量基因和蛋白质的研究。我们表明，SCS使用DTMP方法强烈影响神经元和胶质细胞特异性转录组的表达，同时调节它们向健康动物的表达水平。DTMP调节受疼痛影响的神经胶质介导过程中的关键基因和蛋白质的能力表明，在未受伤的动物中发现的水平，在神经胶质细胞环境促进镇痛的转变。
Glial cells play an essential role in maintaining the proper functioning of the nervous system. They are more abundant than neurons in most neural tissues and provide metabolic and catabolic regulation, maintaining the homeostatic balance at the synapse. Chronic pain is generated and sustained by the disruption of glia-mediated processes in the central nervous system resulting in unbalanced neuron–glial interactions. Animal models of neuropathic pain have been used to demonstrate that changes in immune and neuroinflammatory processes occur in the course of pain chronification. Spinal cord stimulation (SCS) is an electrical neuromodulation therapy proven safe and effective for treating intractable chronic pain. Traditional SCS therapies were developed based on the gate control theory of pain and rely on stimulating large Aβ neurons to induce paresthesia in the painful dermatome intended to mask nociceptive input carried out by small sensory neurons. A paradigm shift was introduced with SCS treatments that do not require paresthesia to provide effective pain relief. Efforts to understand the mechanism of action of SCS have considered the role of glial cells and the effect of electrical parameters on neuron–glial interactions. Recent work has provided evidence that SCS affects expression levels of glia-related genes and proteins. This inspired the development of a differential target multiplexed programming (DTMP) approach using electrical signals that can rebalance neuroglial interactions by targeting neurons and glial cells differentially. Our group pioneered the utilization of transcriptomic and proteomic analyses to identify the mechanism of action by which SCS works, emphasizing the DTMP approach. This is an account of evidence demonstrating the effect of SCS on glia-mediated processes using neuropathic pain models, emphasizing studies that rely on the evaluation of large sets of genes and proteins. We show that SCS using a DTMP approach strongly affects the expression of neuron and glia-specific transcriptomes while modulating them toward expression levels of healthy animals. The ability of DTMP to modulate key genes and proteins involved in glia-mediated processes affected by pain toward levels found in uninjured animals demonstrates a shift in the neuron–glial environment promoting analgesia.
登录
查看更多内容
影响因子：
56.9
作者：
MELZACK, R;WALL, PD
通讯作者：
WALL, PD
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
8.8
作者：
Kapural, Leonardo;Yu, Cong;Burgher, Abram H.
通讯作者：
Burgher, Abram H.
影响因子：
2.6
作者：
Fishman, Michael A.;Calodney, Aaron;Vallejo, Ricardo
通讯作者：
Vallejo, Ricardo
影响因子：
2.8
作者：
Deer, Timothy R.;Mekhail, Nagy;North, Richard
通讯作者：
North, Richard