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

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-...

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Veröffentlicht in:MOLECULAR PAIN 2018, Vol.14, p.1744806918817429-1744806918817429
Hauptverfasser: Stephens, Kimberly E, Chen, Zhiyong, Sivanesan, Eellan, Raja, Srinivasa N, Linderoth, Bengt, Taverna, Sean D, Guan, Yun
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Chen, Zhiyong
Sivanesan, Eellan
Raja, Srinivasa N
Linderoth, Bengt
Taverna, Sean D
Guan, Yun
description 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.
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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. 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subjects Animals
Cell activation
Cell surface
Chronic Disease
Chronic pain
Constriction, Pathologic
Down-Regulation - genetics
Drug therapy
Female
Gene Expression Profiling
Gene Ontology
Immune response
Male
Models, Biological
Neuralgia
Neuralgia - genetics
Neuralgia - pathology
Pain
Rats, Sprague-Dawley
Ribonucleic acid
RNA
Sciatic nerve
Sciatic Nerve - injuries
Sciatic Nerve - metabolism
Sciatic Nerve - pathology
Sequence Analysis, RNA
Sex Characteristics
Spinal cord
Spinal Cord - metabolism
Spinal cord injuries
Spinal Cord Stimulation
Synapses - metabolism
Synaptic density
Transcription
Up-Regulation - genetics
title RNA-seq of spinal cord from nerve-injured rats after spinal cord stimulation
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