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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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. 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.</description><identifier>ISSN: 1744-8069</identifier><identifier>EISSN: 1744-8069</identifier><identifier>DOI: 10.1177/1744806918817429</identifier><identifier>PMID: 30451078</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>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</subject><ispartof>MOLECULAR PAIN, 2018, Vol.14, p.1744806918817429-1744806918817429</ispartof><rights>The Author(s) 2018</rights><rights>The Author(s) 2018. This work is licensed under the Creative Commons Attribution – Non-Commercial License http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2018 2018 SAGE Publications Inc., unless otherwise noted. Manuscript content on this site is licensed under Creative Commons Licenses</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c566t-58f6e1f5b0ed5d6a169fdfab60bfb2106beba569a32c69ba454499519e7f0d0d3</citedby><cites>FETCH-LOGICAL-c566t-58f6e1f5b0ed5d6a169fdfab60bfb2106beba569a32c69ba454499519e7f0d0d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6293371/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6293371/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,551,724,777,781,882,4010,21947,27834,27904,27905,27906,44926,45314,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30451078$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:139755027$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Stephens, Kimberly E</creatorcontrib><creatorcontrib>Chen, Zhiyong</creatorcontrib><creatorcontrib>Sivanesan, Eellan</creatorcontrib><creatorcontrib>Raja, Srinivasa N</creatorcontrib><creatorcontrib>Linderoth, Bengt</creatorcontrib><creatorcontrib>Taverna, Sean D</creatorcontrib><creatorcontrib>Guan, Yun</creatorcontrib><title>RNA-seq of spinal cord from nerve-injured rats after spinal cord stimulation</title><title>MOLECULAR PAIN</title><addtitle>Mol Pain</addtitle><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.</description><subject>Animals</subject><subject>Cell activation</subject><subject>Cell surface</subject><subject>Chronic Disease</subject><subject>Chronic pain</subject><subject>Constriction, Pathologic</subject><subject>Down-Regulation - genetics</subject><subject>Drug therapy</subject><subject>Female</subject><subject>Gene Expression Profiling</subject><subject>Gene Ontology</subject><subject>Immune response</subject><subject>Male</subject><subject>Models, Biological</subject><subject>Neuralgia</subject><subject>Neuralgia - genetics</subject><subject>Neuralgia - pathology</subject><subject>Pain</subject><subject>Rats, Sprague-Dawley</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Sciatic nerve</subject><subject>Sciatic Nerve - injuries</subject><subject>Sciatic Nerve - metabolism</subject><subject>Sciatic Nerve - pathology</subject><subject>Sequence Analysis, RNA</subject><subject>Sex Characteristics</subject><subject>Spinal cord</subject><subject>Spinal Cord - metabolism</subject><subject>Spinal cord injuries</subject><subject>Spinal Cord Stimulation</subject><subject>Synapses - metabolism</subject><subject>Synaptic density</subject><subject>Transcription</subject><subject>Up-Regulation - genetics</subject><issn>1744-8069</issn><issn>1744-8069</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>AFRWT</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>D8T</sourceid><recordid>eNp1kUtLxDAUhYMovveupODGTTVpXs1GEPEFg4LoOqTtzdixbcakVfz3ZphRZwZc5XDvd0-SexA6IviMECnPiWQsx0KRPI8yUxtod1ZKZ7XNJb2D9kKYYEwlFmQb7VDMOMEy30Wjp4fLNMB74mwSpnVnmqR0vkqsd23Sgf-AtO4mg4cq8aYPibE9-BUy9HU7NKavXXeAtqxpAhwuzn30cnP9fHWXjh5v768uR2nJhehTnlsBxPICQ8UrYYhQtrKmELiwRUawKKAwXChDs1KowjDOmFKcKJAWV7ii-yid-4ZPmA6Fnvq6Nf5LO1PrRektKtAsZ5jJyF_M-dhpoSqh671pVsZWO139qsfuQ4tMUSpJNDhdGHj3PkDodVuHEprGdOCGoDNCuaAyYzSiJ2voxA0-bitSjMWMFKN5pPCcKr0LwYP9fQzBehatXo82jhwvf-J34CfLpa2YMfzd-q_hN1-zrMA</recordid><startdate>2018</startdate><enddate>2018</enddate><creator>Stephens, Kimberly E</creator><creator>Chen, Zhiyong</creator><creator>Sivanesan, Eellan</creator><creator>Raja, Srinivasa N</creator><creator>Linderoth, Bengt</creator><creator>Taverna, Sean D</creator><creator>Guan, Yun</creator><general>SAGE Publications</general><general>Sage Publications Ltd</general><scope>AFRWT</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>2018</creationdate><title>RNA-seq of spinal cord from nerve-injured rats after spinal cord stimulation</title><author>Stephens, Kimberly E ; Chen, Zhiyong ; Sivanesan, Eellan ; Raja, Srinivasa N ; Linderoth, Bengt ; Taverna, Sean D ; Guan, Yun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c566t-58f6e1f5b0ed5d6a169fdfab60bfb2106beba569a32c69ba454499519e7f0d0d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Cell activation</topic><topic>Cell surface</topic><topic>Chronic Disease</topic><topic>Chronic pain</topic><topic>Constriction, Pathologic</topic><topic>Down-Regulation - genetics</topic><topic>Drug therapy</topic><topic>Female</topic><topic>Gene Expression Profiling</topic><topic>Gene Ontology</topic><topic>Immune response</topic><topic>Male</topic><topic>Models, Biological</topic><topic>Neuralgia</topic><topic>Neuralgia - genetics</topic><topic>Neuralgia - pathology</topic><topic>Pain</topic><topic>Rats, Sprague-Dawley</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>Sciatic nerve</topic><topic>Sciatic Nerve - injuries</topic><topic>Sciatic Nerve - metabolism</topic><topic>Sciatic Nerve - pathology</topic><topic>Sequence Analysis, RNA</topic><topic>Sex Characteristics</topic><topic>Spinal cord</topic><topic>Spinal Cord - metabolism</topic><topic>Spinal cord injuries</topic><topic>Spinal Cord Stimulation</topic><topic>Synapses - metabolism</topic><topic>Synaptic density</topic><topic>Transcription</topic><topic>Up-Regulation - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stephens, Kimberly E</creatorcontrib><creatorcontrib>Chen, Zhiyong</creatorcontrib><creatorcontrib>Sivanesan, Eellan</creatorcontrib><creatorcontrib>Raja, Srinivasa N</creatorcontrib><creatorcontrib>Linderoth, Bengt</creatorcontrib><creatorcontrib>Taverna, Sean D</creatorcontrib><creatorcontrib>Guan, Yun</creatorcontrib><collection>Sage Journals GOLD Open Access 2024</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>MOLECULAR PAIN</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stephens, Kimberly E</au><au>Chen, Zhiyong</au><au>Sivanesan, Eellan</au><au>Raja, Srinivasa N</au><au>Linderoth, Bengt</au><au>Taverna, Sean D</au><au>Guan, Yun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>RNA-seq of spinal cord from nerve-injured rats after spinal cord stimulation</atitle><jtitle>MOLECULAR PAIN</jtitle><addtitle>Mol Pain</addtitle><date>2018</date><risdate>2018</risdate><volume>14</volume><spage>1744806918817429</spage><epage>1744806918817429</epage><pages>1744806918817429-1744806918817429</pages><issn>1744-8069</issn><eissn>1744-8069</eissn><abstract>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.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>30451078</pmid><doi>10.1177/1744806918817429</doi><oa>free_for_read</oa></addata></record> |
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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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