Intrathecal transplantation of autologous macrophages genetically modified to secrete proenkephalin ameliorated hyperalgesia and allodynia following peripheral nerve injury in rats
To develop a novel genetic approach for the treatment of pain, we tested the transplantation of gene-transferred autologous macrophages by lumbar puncture. A rat neuropathic pain model was produced by chronic constriction of the sciatic nerve. Autologous macrophages were collected from the intraperi...
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Veröffentlicht in: | Neuroscience research 2009-05, Vol.64 (1), p.56-62 |
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description | To develop a novel genetic approach for the treatment of pain, we tested the transplantation of gene-transferred autologous macrophages by lumbar puncture. A rat neuropathic pain model was produced by chronic constriction of the sciatic nerve. Autologous macrophages were collected from the intraperitoneal space. Then human proenkephalin gene was transferred into the macrophages by electroporation. The gene-transferred macrophages were transplanted into the subarachnoid space by lumbar puncture. One week after transplantation, the heat hyperalgesia and allodynia induced by sciatic nerve constriction completely remitted. The analgesic action continued until at least 4 weeks after transplantation. The transplanted macrophages migrated into the spinal cord and expressed proenkephalin mRNA and Met-enkephalin protein. The method we tested in the present study may be a safe, simple and effective way to inhibit pain sensation after peripheral nerve injuries. |
doi_str_mv | 10.1016/j.neures.2009.01.011 |
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A rat neuropathic pain model was produced by chronic constriction of the sciatic nerve. Autologous macrophages were collected from the intraperitoneal space. Then human proenkephalin gene was transferred into the macrophages by electroporation. The gene-transferred macrophages were transplanted into the subarachnoid space by lumbar puncture. One week after transplantation, the heat hyperalgesia and allodynia induced by sciatic nerve constriction completely remitted. The analgesic action continued until at least 4 weeks after transplantation. The transplanted macrophages migrated into the spinal cord and expressed proenkephalin mRNA and Met-enkephalin protein. The method we tested in the present study may be a safe, simple and effective way to inhibit pain sensation after peripheral nerve injuries.</description><identifier>ISSN: 0168-0102</identifier><identifier>EISSN: 1872-8111</identifier><identifier>DOI: 10.1016/j.neures.2009.01.011</identifier><identifier>PMID: 19428684</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>Allodynia ; Animals ; Cells, Cultured ; Enkephalin, Methionine - metabolism ; Enkephalins - metabolism ; Gene transfer ; Hot Temperature ; Humans ; Hyperalgesia ; Hyperalgesia - etiology ; Hyperalgesia - physiopathology ; Hyperalgesia - therapy ; Injections, Spinal ; Macrophage ; Macrophages - physiology ; Macrophages - transplantation ; Male ; Neuropathic pain ; Pain - etiology ; Pain - physiopathology ; Pain Management ; Pain Measurement ; Proenkephalin ; Protein Precursors - metabolism ; Rats ; Rats, Wistar ; RNA, Messenger - metabolism ; Sciatic Neuropathy - complications ; Sciatic Neuropathy - physiopathology ; Sciatic Neuropathy - therapy ; Spinal Cord - physiopathology ; Time Factors ; Transfection ; Transplantation, Autologous</subject><ispartof>Neuroscience research, 2009-05, Vol.64 (1), p.56-62</ispartof><rights>2009 Elsevier Ireland Ltd and the Japan Neuroscience Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c507t-b4d83ea24a3cf9e3288ddeffd631fb19aad6acbe270585171900290a1a295fd3</citedby><cites>FETCH-LOGICAL-c507t-b4d83ea24a3cf9e3288ddeffd631fb19aad6acbe270585171900290a1a295fd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0168010209000339$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19428684$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hino, Masayuki</creatorcontrib><creatorcontrib>Ogata, Tadanori</creatorcontrib><creatorcontrib>Morino, Tadao</creatorcontrib><creatorcontrib>Horiuchi, Hideki</creatorcontrib><creatorcontrib>Yamamoto, Haruyasu</creatorcontrib><title>Intrathecal transplantation of autologous macrophages genetically modified to secrete proenkephalin ameliorated hyperalgesia and allodynia following peripheral nerve injury in rats</title><title>Neuroscience research</title><addtitle>Neurosci Res</addtitle><description>To develop a novel genetic approach for the treatment of pain, we tested the transplantation of gene-transferred autologous macrophages by lumbar puncture. A rat neuropathic pain model was produced by chronic constriction of the sciatic nerve. Autologous macrophages were collected from the intraperitoneal space. Then human proenkephalin gene was transferred into the macrophages by electroporation. The gene-transferred macrophages were transplanted into the subarachnoid space by lumbar puncture. One week after transplantation, the heat hyperalgesia and allodynia induced by sciatic nerve constriction completely remitted. The analgesic action continued until at least 4 weeks after transplantation. The transplanted macrophages migrated into the spinal cord and expressed proenkephalin mRNA and Met-enkephalin protein. The method we tested in the present study may be a safe, simple and effective way to inhibit pain sensation after peripheral nerve injuries.</description><subject>Allodynia</subject><subject>Animals</subject><subject>Cells, Cultured</subject><subject>Enkephalin, Methionine - metabolism</subject><subject>Enkephalins - metabolism</subject><subject>Gene transfer</subject><subject>Hot Temperature</subject><subject>Humans</subject><subject>Hyperalgesia</subject><subject>Hyperalgesia - etiology</subject><subject>Hyperalgesia - physiopathology</subject><subject>Hyperalgesia - therapy</subject><subject>Injections, Spinal</subject><subject>Macrophage</subject><subject>Macrophages - physiology</subject><subject>Macrophages - transplantation</subject><subject>Male</subject><subject>Neuropathic pain</subject><subject>Pain - etiology</subject><subject>Pain - physiopathology</subject><subject>Pain Management</subject><subject>Pain Measurement</subject><subject>Proenkephalin</subject><subject>Protein Precursors - metabolism</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>RNA, Messenger - metabolism</subject><subject>Sciatic Neuropathy - complications</subject><subject>Sciatic Neuropathy - physiopathology</subject><subject>Sciatic Neuropathy - therapy</subject><subject>Spinal Cord - physiopathology</subject><subject>Time Factors</subject><subject>Transfection</subject><subject>Transplantation, Autologous</subject><issn>0168-0102</issn><issn>1872-8111</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc2KVDEQhYMoTjv6BiJZues2yf1LNoIM_gwMuJl9SCeV7rT3Jtckd-S-lw9oNd3gTqGgKvDVKXIOIW8523HG-w-nXYQlQ9kJxtSOcSz-jGy4HMRWcs6fkw1icss4EzfkVSknxlij2uYlueGqFbKX7Yb8vo81m3oEa0aKUyzzaGI1NaRIk6dmqWlMh7QUOhmb03w0Byj0ABFqwJ1xpVNywQdwtCZawGaoQOecIP4ApMcQqZlgDAnPIHRcZ8hmRJFgqImOokZya8SXTzj-CvFAEQnz8czRCPkJaIinJa_YKKqU1-SFN2OBN9d-Sx6_fH68-7Z9-P71_u7Tw9Z2bKjbfetkA0a0prFeQSOkdA68d33D_Z4rY1xv7B7EwDrZ8YErxoRihhuhOu-aW_L-Iou_-blAqXoKxcKIBgEaovtBiE518r-gYLIXSg4IthcQnSwlg9dzDpPJq-ZMn1PVJ31JVZ9T1YxjcVx7d9Vf9hO4v0vXGBH4eAEA3XgKkHWxAaIFFzLYql0K_77wB-MtvMU</recordid><startdate>20090501</startdate><enddate>20090501</enddate><creator>Hino, Masayuki</creator><creator>Ogata, Tadanori</creator><creator>Morino, Tadao</creator><creator>Horiuchi, Hideki</creator><creator>Yamamoto, Haruyasu</creator><general>Elsevier Ireland Ltd</general><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>7QO</scope><scope>7T5</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20090501</creationdate><title>Intrathecal transplantation of autologous macrophages genetically modified to secrete proenkephalin ameliorated hyperalgesia and allodynia following peripheral nerve injury in rats</title><author>Hino, Masayuki ; Ogata, Tadanori ; Morino, Tadao ; Horiuchi, Hideki ; Yamamoto, Haruyasu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c507t-b4d83ea24a3cf9e3288ddeffd631fb19aad6acbe270585171900290a1a295fd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Allodynia</topic><topic>Animals</topic><topic>Cells, Cultured</topic><topic>Enkephalin, Methionine - metabolism</topic><topic>Enkephalins - metabolism</topic><topic>Gene transfer</topic><topic>Hot Temperature</topic><topic>Humans</topic><topic>Hyperalgesia</topic><topic>Hyperalgesia - etiology</topic><topic>Hyperalgesia - physiopathology</topic><topic>Hyperalgesia - therapy</topic><topic>Injections, Spinal</topic><topic>Macrophage</topic><topic>Macrophages - physiology</topic><topic>Macrophages - transplantation</topic><topic>Male</topic><topic>Neuropathic pain</topic><topic>Pain - etiology</topic><topic>Pain - physiopathology</topic><topic>Pain Management</topic><topic>Pain Measurement</topic><topic>Proenkephalin</topic><topic>Protein Precursors - metabolism</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>RNA, Messenger - metabolism</topic><topic>Sciatic Neuropathy - complications</topic><topic>Sciatic Neuropathy - physiopathology</topic><topic>Sciatic Neuropathy - therapy</topic><topic>Spinal Cord - physiopathology</topic><topic>Time Factors</topic><topic>Transfection</topic><topic>Transplantation, Autologous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hino, Masayuki</creatorcontrib><creatorcontrib>Ogata, Tadanori</creatorcontrib><creatorcontrib>Morino, Tadao</creatorcontrib><creatorcontrib>Horiuchi, Hideki</creatorcontrib><creatorcontrib>Yamamoto, Haruyasu</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Neuroscience research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hino, Masayuki</au><au>Ogata, Tadanori</au><au>Morino, Tadao</au><au>Horiuchi, Hideki</au><au>Yamamoto, Haruyasu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intrathecal transplantation of autologous macrophages genetically modified to secrete proenkephalin ameliorated hyperalgesia and allodynia following peripheral nerve injury in rats</atitle><jtitle>Neuroscience research</jtitle><addtitle>Neurosci Res</addtitle><date>2009-05-01</date><risdate>2009</risdate><volume>64</volume><issue>1</issue><spage>56</spage><epage>62</epage><pages>56-62</pages><issn>0168-0102</issn><eissn>1872-8111</eissn><abstract>To develop a novel genetic approach for the treatment of pain, we tested the transplantation of gene-transferred autologous macrophages by lumbar puncture. A rat neuropathic pain model was produced by chronic constriction of the sciatic nerve. Autologous macrophages were collected from the intraperitoneal space. Then human proenkephalin gene was transferred into the macrophages by electroporation. The gene-transferred macrophages were transplanted into the subarachnoid space by lumbar puncture. One week after transplantation, the heat hyperalgesia and allodynia induced by sciatic nerve constriction completely remitted. The analgesic action continued until at least 4 weeks after transplantation. The transplanted macrophages migrated into the spinal cord and expressed proenkephalin mRNA and Met-enkephalin protein. The method we tested in the present study may be a safe, simple and effective way to inhibit pain sensation after peripheral nerve injuries.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>19428684</pmid><doi>10.1016/j.neures.2009.01.011</doi><tpages>7</tpages></addata></record> |
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subjects | Allodynia Animals Cells, Cultured Enkephalin, Methionine - metabolism Enkephalins - metabolism Gene transfer Hot Temperature Humans Hyperalgesia Hyperalgesia - etiology Hyperalgesia - physiopathology Hyperalgesia - therapy Injections, Spinal Macrophage Macrophages - physiology Macrophages - transplantation Male Neuropathic pain Pain - etiology Pain - physiopathology Pain Management Pain Measurement Proenkephalin Protein Precursors - metabolism Rats Rats, Wistar RNA, Messenger - metabolism Sciatic Neuropathy - complications Sciatic Neuropathy - physiopathology Sciatic Neuropathy - therapy Spinal Cord - physiopathology Time Factors Transfection Transplantation, Autologous |
title | Intrathecal transplantation of autologous macrophages genetically modified to secrete proenkephalin ameliorated hyperalgesia and allodynia following peripheral nerve injury in rats |
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