RNA-seq of spinal cord from nerve-injured rats after spinal cord stimulation

被引:36
|
作者
Stephens, Kimberly E. [1 ,2 ,3 ]
Chen, Zhiyong [3 ,4 ]
Sivanesan, Eellan [3 ]
Raja, Srinivasa N. [3 ]
Linderoth, Bengt [5 ]
Taverna, Sean D. [1 ,2 ]
Guan, Yun [3 ,6 ]
机构
[1] Johns Hopkins Univ, Dept Pharmacol & Mol Sci, Sch Med, Baltimore, MA USA
[2] Johns Hopkins Univ, Ctr Epigenet, Sch Med, Baltimore, MA USA
[3] Johns Hopkins Univ, Sch Med, Dept Anesthesia & Crit Care Med, Baltimore, MA USA
[4] Chinese Acad Med Sci, Inst Basic Med Sci, Dept Human Anat Histol & Embryol, Peking Union Med Coll,Sch Basic Med,Neurosci Ctr, Beijing, Peoples R China
[5] Karolinska Inst, Div Funct Neurosurg, Dept Clin Neurosci, Stockholm, Sweden
[6] Johns Hopkins Univ, Sch Med, Dept Neurol Surg, Baltimore, MA USA
基金
美国国家卫生研究院;
关键词
RNA-seq; gene expression; spinal cord stimulation; nerve injury; pain; spinal cord; POSTSYNAPTIC DENSITY PROTEIN; NEUROPATHIC PAIN; NMDA RECEPTOR; MECHANICAL HYPERSENSITIVITY; DEPENDENT INHIBITION; SAFE PRINCIPLES; DORSAL-COLUMN; ANIMAL-MODEL; HYPERALGESIA; ALGORITHMS;
D O I
10.1177/1744806918817429
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Spinal cord stimulation has become an important modality in pain treatment especially for neuropathic pain conditions refractory to pharmacotherapy. However, the molecular control of inhibitory and excitatory mechanisms observed after spinal cord stimulation are poorly understood. Here, we used RNA-seq to identify differences in the expression of genes and gene networks in spinal cord tissue from nerve-injured rats with and without repetitive conventional spinal cord stimulation treatment. Five weeks after chronic constrictive injury to the left sciatic nerve, male and female rats were randomized to receive repetitive spinal cord stimulation or no treatment. Rats receiving spinal cord stimulation underwent epidural placement of a miniature stimulating electrode and received seven sessions of spinal cord stimulation (50 Hz, 80% motor threshold, 0.2 ms, constant current bipolar stimulation, 120 min/session) over four consecutive days. Within 2 h after the last spinal cord stimulation treatment, the L4-L6 spinal segments ipsilateral to the side of nerve injury were harvested and used to generate libraries for RNA-seq. Our RNA-seq data suggest further increases of many existing upregulated immune responses in chronic constrictive injury rats after repetitive spinal cord stimulation, including transcription of cell surface receptors and activation of non-neuronal cells. We also demonstrate that repetitive spinal cord stimulation represses transcription of several key synaptic signaling genes that encode scaffold proteins in the post-synaptic density. Our transcriptional studies suggest a potential relationship between specific genes and the therapeutic effects observed in patients undergoing conventional spinal cord stimulation after nerve injury. Furthermore, our results may help identify new therapeutic targets for improving the efficacy of conventional spinal cord stimulation and other chronic pain treatments.
引用
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页数:13
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