Antiallodynic effects of propentofylline Elicited by interrupting spinal glial function in a rat model of bone cancer pain
The activation of microglia and astrocytes in the spinal cord is involved in the progress of cancer pain. Propentofylline (PPF), a glial modulating agent, alleviates pain hypersensitivity in neuropathic pain models. The present study investigated the potential roles of PPF in a preclinical rat model...
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| Veröffentlicht in: | Journal of neuroscience research 2011-11, Vol.89 (11), p.1877-1886 |
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| creator | Yao, Ming Chang, Xiang-yang Chu, Yu-xia Yang, Jian-ping Wang, Li-na Cao, Hao-qiang Liu, Ming-juan Xu, Qi-nian |
| description | The activation of microglia and astrocytes in the spinal cord is involved in the progress of cancer pain. Propentofylline (PPF), a glial modulating agent, alleviates pain hypersensitivity in neuropathic pain models. The present study investigated the potential roles of PPF in a preclinical rat model of bone caner pain established by inoculating Walker 256 cells into the left tibia. At day 9 postinoculation, single administration of PPF (10 μg/10 μl, i.t.) significantly but transiently suppressed mechanical allodynia induced by bone cancer. Repeated application of PPF (10 μg/10 μl, i.t., once daily from days 9 to 12) persistently relieved mechanical allodynia on the side ipsilateral to surgery. Immunohistochemistry and ELISA showed that microglia and astrocytes in the spinal cord were activated, and the production of glia‐derived proinflammatory cytokines interleukin‐1β (IL‐1β), IL‐6, and tumor necrosis factor‐α (TNF‐α) markedly increased at day 12 postinoculation in the cancer group. Intrathecal injection of PPF (10 μg/10 μl) significantly inhibited the activation of spinal glial cells and the expression of proinflammatory cytokines. These results suggest that the glial modulating agent PPF has antiallodynic effects on bone cancer pain and has potential utility for clinical treatment of cancer pain. © 2011 Wiley‐Liss, Inc. |
| doi_str_mv | 10.1002/jnr.22711 |
| format | Article |
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Propentofylline (PPF), a glial modulating agent, alleviates pain hypersensitivity in neuropathic pain models. The present study investigated the potential roles of PPF in a preclinical rat model of bone caner pain established by inoculating Walker 256 cells into the left tibia. At day 9 postinoculation, single administration of PPF (10 μg/10 μl, i.t.) significantly but transiently suppressed mechanical allodynia induced by bone cancer. Repeated application of PPF (10 μg/10 μl, i.t., once daily from days 9 to 12) persistently relieved mechanical allodynia on the side ipsilateral to surgery. Immunohistochemistry and ELISA showed that microglia and astrocytes in the spinal cord were activated, and the production of glia‐derived proinflammatory cytokines interleukin‐1β (IL‐1β), IL‐6, and tumor necrosis factor‐α (TNF‐α) markedly increased at day 12 postinoculation in the cancer group. Intrathecal injection of PPF (10 μg/10 μl) significantly inhibited the activation of spinal glial cells and the expression of proinflammatory cytokines. These results suggest that the glial modulating agent PPF has antiallodynic effects on bone cancer pain and has potential utility for clinical treatment of cancer pain. © 2011 Wiley‐Liss, Inc.</description><identifier>ISSN: 0360-4012</identifier><identifier>ISSN: 1097-4547</identifier><identifier>EISSN: 1097-4547</identifier><identifier>DOI: 10.1002/jnr.22711</identifier><identifier>PMID: 21812015</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Animals ; Bone Neoplasms - complications ; Bone Neoplasms - metabolism ; Bone Neoplasms - physiopathology ; cytokines ; Cytokines - metabolism ; Disease Models, Animal ; Female ; glial cells ; Neuroglia - drug effects ; Neuroglia - metabolism ; pain ; Pain - drug therapy ; Pain - etiology ; Pain - metabolism ; Pain - physiopathology ; Rats ; Rats, Sprague-Dawley ; spinal cord ; Spinal Cord - drug effects ; Spinal Cord - metabolism ; Spinal Cord - physiopathology ; Xanthines - therapeutic use</subject><ispartof>Journal of neuroscience research, 2011-11, Vol.89 (11), p.1877-1886</ispartof><rights>Copyright © 2011 Wiley‐Liss, Inc.</rights><rights>Copyright © 2011 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3951-c05552faaa08c426fd98d5a385146f3cadbf6cf8d3e7e0ad0d1b74c025304c693</citedby><cites>FETCH-LOGICAL-c3951-c05552faaa08c426fd98d5a385146f3cadbf6cf8d3e7e0ad0d1b74c025304c693</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjnr.22711$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjnr.22711$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21812015$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yao, Ming</creatorcontrib><creatorcontrib>Chang, Xiang-yang</creatorcontrib><creatorcontrib>Chu, Yu-xia</creatorcontrib><creatorcontrib>Yang, Jian-ping</creatorcontrib><creatorcontrib>Wang, Li-na</creatorcontrib><creatorcontrib>Cao, Hao-qiang</creatorcontrib><creatorcontrib>Liu, Ming-juan</creatorcontrib><creatorcontrib>Xu, Qi-nian</creatorcontrib><title>Antiallodynic effects of propentofylline Elicited by interrupting spinal glial function in a rat model of bone cancer pain</title><title>Journal of neuroscience research</title><addtitle>J. Neurosci. Res</addtitle><description>The activation of microglia and astrocytes in the spinal cord is involved in the progress of cancer pain. Propentofylline (PPF), a glial modulating agent, alleviates pain hypersensitivity in neuropathic pain models. The present study investigated the potential roles of PPF in a preclinical rat model of bone caner pain established by inoculating Walker 256 cells into the left tibia. At day 9 postinoculation, single administration of PPF (10 μg/10 μl, i.t.) significantly but transiently suppressed mechanical allodynia induced by bone cancer. Repeated application of PPF (10 μg/10 μl, i.t., once daily from days 9 to 12) persistently relieved mechanical allodynia on the side ipsilateral to surgery. Immunohistochemistry and ELISA showed that microglia and astrocytes in the spinal cord were activated, and the production of glia‐derived proinflammatory cytokines interleukin‐1β (IL‐1β), IL‐6, and tumor necrosis factor‐α (TNF‐α) markedly increased at day 12 postinoculation in the cancer group. Intrathecal injection of PPF (10 μg/10 μl) significantly inhibited the activation of spinal glial cells and the expression of proinflammatory cytokines. These results suggest that the glial modulating agent PPF has antiallodynic effects on bone cancer pain and has potential utility for clinical treatment of cancer pain. © 2011 Wiley‐Liss, Inc.</description><subject>Animals</subject><subject>Bone Neoplasms - complications</subject><subject>Bone Neoplasms - metabolism</subject><subject>Bone Neoplasms - physiopathology</subject><subject>cytokines</subject><subject>Cytokines - metabolism</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>glial cells</subject><subject>Neuroglia - drug effects</subject><subject>Neuroglia - metabolism</subject><subject>pain</subject><subject>Pain - drug therapy</subject><subject>Pain - etiology</subject><subject>Pain - metabolism</subject><subject>Pain - physiopathology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>spinal cord</subject><subject>Spinal Cord - drug effects</subject><subject>Spinal Cord - metabolism</subject><subject>Spinal Cord - physiopathology</subject><subject>Xanthines - therapeutic use</subject><issn>0360-4012</issn><issn>1097-4547</issn><issn>1097-4547</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90U1vFSEYhmFiNPZYXfgHDDt1Me0LDMPMsmlq9aSpiR_RHWH4aKgcZgpMdPz1Uk_bna7YXNwJPAi9JHBEAOjxdUxHlApCHqENgUE0LW_FY7QB1kHTAqEH6FnO1wAwDJw9RQeU9IQC4Rv0-yQWr0KYzBq9xtY5q0vGk8NzmmYby-TWEHy0-Cx47Ys1eFyxj8WmtMzFxyucZx9VwFehdrBboi5-ipVghZMqeDcZG26D41QrWkVtE56Vj8_RE6dCti_uzkP09d3Zl9P3zcXH8w-nJxeNZgMnjQbOOXVKKeh1Sztnht5wxXpO2s4xrczoOu16w6ywoAwYMopWA-UMWt0N7BC93nfri24Wm4vc-axtCCraacmy7wci-oF2Vb75ryRAxCBo_eFK3-6pTlPOyTo5J79Taa1I3o4i6yjy7yjVvrrLLuPOmgd5v0IFx3vw0we7_rskt5ef7pPN_obPxf56uKHSD9kJJrj8dnkuyXfYbgXZys_sD62Apto</recordid><startdate>201111</startdate><enddate>201111</enddate><creator>Yao, Ming</creator><creator>Chang, Xiang-yang</creator><creator>Chu, Yu-xia</creator><creator>Yang, Jian-ping</creator><creator>Wang, Li-na</creator><creator>Cao, Hao-qiang</creator><creator>Liu, Ming-juan</creator><creator>Xu, Qi-nian</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</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>7QP</scope><scope>7TK</scope><scope>7X8</scope></search><sort><creationdate>201111</creationdate><title>Antiallodynic effects of propentofylline Elicited by interrupting spinal glial function in a rat model of bone cancer pain</title><author>Yao, Ming ; Chang, Xiang-yang ; Chu, Yu-xia ; Yang, Jian-ping ; Wang, Li-na ; Cao, Hao-qiang ; Liu, Ming-juan ; Xu, Qi-nian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3951-c05552faaa08c426fd98d5a385146f3cadbf6cf8d3e7e0ad0d1b74c025304c693</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Bone Neoplasms - complications</topic><topic>Bone Neoplasms - metabolism</topic><topic>Bone Neoplasms - physiopathology</topic><topic>cytokines</topic><topic>Cytokines - metabolism</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>glial cells</topic><topic>Neuroglia - drug effects</topic><topic>Neuroglia - metabolism</topic><topic>pain</topic><topic>Pain - drug therapy</topic><topic>Pain - etiology</topic><topic>Pain - metabolism</topic><topic>Pain - physiopathology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>spinal cord</topic><topic>Spinal Cord - drug effects</topic><topic>Spinal Cord - metabolism</topic><topic>Spinal Cord - physiopathology</topic><topic>Xanthines - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yao, Ming</creatorcontrib><creatorcontrib>Chang, Xiang-yang</creatorcontrib><creatorcontrib>Chu, Yu-xia</creatorcontrib><creatorcontrib>Yang, Jian-ping</creatorcontrib><creatorcontrib>Wang, Li-na</creatorcontrib><creatorcontrib>Cao, Hao-qiang</creatorcontrib><creatorcontrib>Liu, Ming-juan</creatorcontrib><creatorcontrib>Xu, Qi-nian</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neuroscience research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yao, Ming</au><au>Chang, Xiang-yang</au><au>Chu, Yu-xia</au><au>Yang, Jian-ping</au><au>Wang, Li-na</au><au>Cao, Hao-qiang</au><au>Liu, Ming-juan</au><au>Xu, Qi-nian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antiallodynic effects of propentofylline Elicited by interrupting spinal glial function in a rat model of bone cancer pain</atitle><jtitle>Journal of neuroscience research</jtitle><addtitle>J. Neurosci. Res</addtitle><date>2011-11</date><risdate>2011</risdate><volume>89</volume><issue>11</issue><spage>1877</spage><epage>1886</epage><pages>1877-1886</pages><issn>0360-4012</issn><issn>1097-4547</issn><eissn>1097-4547</eissn><abstract>The activation of microglia and astrocytes in the spinal cord is involved in the progress of cancer pain. Propentofylline (PPF), a glial modulating agent, alleviates pain hypersensitivity in neuropathic pain models. The present study investigated the potential roles of PPF in a preclinical rat model of bone caner pain established by inoculating Walker 256 cells into the left tibia. At day 9 postinoculation, single administration of PPF (10 μg/10 μl, i.t.) significantly but transiently suppressed mechanical allodynia induced by bone cancer. Repeated application of PPF (10 μg/10 μl, i.t., once daily from days 9 to 12) persistently relieved mechanical allodynia on the side ipsilateral to surgery. Immunohistochemistry and ELISA showed that microglia and astrocytes in the spinal cord were activated, and the production of glia‐derived proinflammatory cytokines interleukin‐1β (IL‐1β), IL‐6, and tumor necrosis factor‐α (TNF‐α) markedly increased at day 12 postinoculation in the cancer group. Intrathecal injection of PPF (10 μg/10 μl) significantly inhibited the activation of spinal glial cells and the expression of proinflammatory cytokines. These results suggest that the glial modulating agent PPF has antiallodynic effects on bone cancer pain and has potential utility for clinical treatment of cancer pain. © 2011 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>21812015</pmid><doi>10.1002/jnr.22711</doi><tpages>10</tpages></addata></record> |
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| subjects | Animals Bone Neoplasms - complications Bone Neoplasms - metabolism Bone Neoplasms - physiopathology cytokines Cytokines - metabolism Disease Models, Animal Female glial cells Neuroglia - drug effects Neuroglia - metabolism pain Pain - drug therapy Pain - etiology Pain - metabolism Pain - physiopathology Rats Rats, Sprague-Dawley spinal cord Spinal Cord - drug effects Spinal Cord - metabolism Spinal Cord - physiopathology Xanthines - therapeutic use |
| title | Antiallodynic effects of propentofylline Elicited by interrupting spinal glial function in a rat model of bone cancer pain |
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