P-Rex2 mediation of synaptic plasticity contributes to bone cancer pain
Bone cancer pain (BCP) seriously affects the quality of life; however, due to its complex mechanism, the clinical treatment was unsatisfactory. Recent studies have showed several Rac-specific guanine nucleotide exchange factors (GEFs) that affect development and structure of neuronal processes play...
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| Veröffentlicht in: | Molecular pain 2022-02, Vol.18, p.17448069221076460-17448069221076460 |
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| creator | Fu, Qiaochu Huang, Xiaoxia Wan, Shengjun Li, Yang Li, Xiaohui Su, Shanchun Xu, Xueqin Wu, Yanqiong |
| description | Bone cancer pain (BCP) seriously affects the quality of life; however, due to its complex mechanism, the clinical treatment was unsatisfactory. Recent studies have showed several Rac-specific guanine nucleotide exchange factors (GEFs) that affect development and structure of neuronal processes play a vital role in the regulation of chronic pain. P-Rex2 is one of GEFs that regulate spine density, and the present study was performed to examine the effect of P-Rex2 on the development of BCP. Tumor cells implantation induced the mechanical hyperalgesia, which was accompanied by an increase in spinal protein P-Rex2, phosphorylated Rac1 (p-Rac1) and phosphorylated GluR1 (p-GluR1), and number of spines. Intrathecal injection a P-Rex2-targeting RNAi lentivirus relieved BCP and reduced the expression of P-Rex2, p-Rac1, p-GluR1, and number of spines in the BCP mice. Meanwhile, P-Rex2 knockdown reversed BCP-enhanced AMPA receptor (AMPAR)-induced current in dorsal horn neurons. In summary, this study suggested that P-Rex2 regulated GluR1-containing AMPAR trafficking and spine morphology via Rac1/pGluR1 pathway is a fundamental pathogenesis of BCP. Our findings provide a better understanding of the function of P-Rex2 as a possible therapeutic target for relieving BCP. |
| doi_str_mv | 10.1177/17448069221076460 |
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Recent studies have showed several Rac-specific guanine nucleotide exchange factors (GEFs) that affect development and structure of neuronal processes play a vital role in the regulation of chronic pain. P-Rex2 is one of GEFs that regulate spine density, and the present study was performed to examine the effect of P-Rex2 on the development of BCP. Tumor cells implantation induced the mechanical hyperalgesia, which was accompanied by an increase in spinal protein P-Rex2, phosphorylated Rac1 (p-Rac1) and phosphorylated GluR1 (p-GluR1), and number of spines. Intrathecal injection a P-Rex2-targeting RNAi lentivirus relieved BCP and reduced the expression of P-Rex2, p-Rac1, p-GluR1, and number of spines in the BCP mice. Meanwhile, P-Rex2 knockdown reversed BCP-enhanced AMPA receptor (AMPAR)-induced current in dorsal horn neurons. In summary, this study suggested that P-Rex2 regulated GluR1-containing AMPAR trafficking and spine morphology via Rac1/pGluR1 pathway is a fundamental pathogenesis of BCP. Our findings provide a better understanding of the function of P-Rex2 as a possible therapeutic target for relieving BCP.</description><identifier>ISSN: 1744-8069</identifier><identifier>EISSN: 1744-8069</identifier><identifier>DOI: 10.1177/17448069221076460</identifier><identifier>PMID: 35083941</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>Animals ; Bone cancer ; Bone Neoplasms - complications ; Cancer Pain ; Chronic pain ; Dendritic spines ; Dorsal horn ; Glutamate receptors ; Glutamic acid receptors (ionotropic) ; GTPase-Activating Proteins ; Guanine nucleotide exchange factor ; Guanine Nucleotide Exchange Factors - genetics ; Hyperalgesia ; Mice ; Neuronal Plasticity ; Pain perception ; Quality of Life ; Rac1 protein ; RNA-mediated interference ; Synaptic plasticity ; Therapeutic targets ; Tumor cells ; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid ; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors</subject><ispartof>Molecular pain, 2022-02, Vol.18, p.17448069221076460-17448069221076460</ispartof><rights>The Author(s) 2022</rights><rights>The Author(s) 2022. This work is licensed under the Creative Commons Attribution – Non-Commercial License https://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) 2022 2022 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-c466t-d47a6d6ffd55966bf01b3ee3c022be5fc53d1bdfd105bdb4c7f708708d8cf7c03</citedby><cites>FETCH-LOGICAL-c466t-d47a6d6ffd55966bf01b3ee3c022be5fc53d1bdfd105bdb4c7f708708d8cf7c03</cites><orcidid>0000-0002-3001-0061</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891909/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891909/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,886,21971,27858,27929,27930,44950,45338,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35083941$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fu, Qiaochu</creatorcontrib><creatorcontrib>Huang, Xiaoxia</creatorcontrib><creatorcontrib>Wan, Shengjun</creatorcontrib><creatorcontrib>Li, Yang</creatorcontrib><creatorcontrib>Li, Xiaohui</creatorcontrib><creatorcontrib>Su, Shanchun</creatorcontrib><creatorcontrib>Xu, Xueqin</creatorcontrib><creatorcontrib>Wu, Yanqiong</creatorcontrib><title>P-Rex2 mediation of synaptic plasticity contributes to bone cancer pain</title><title>Molecular pain</title><addtitle>Mol Pain</addtitle><description>Bone cancer pain (BCP) seriously affects the quality of life; however, due to its complex mechanism, the clinical treatment was unsatisfactory. Recent studies have showed several Rac-specific guanine nucleotide exchange factors (GEFs) that affect development and structure of neuronal processes play a vital role in the regulation of chronic pain. P-Rex2 is one of GEFs that regulate spine density, and the present study was performed to examine the effect of P-Rex2 on the development of BCP. Tumor cells implantation induced the mechanical hyperalgesia, which was accompanied by an increase in spinal protein P-Rex2, phosphorylated Rac1 (p-Rac1) and phosphorylated GluR1 (p-GluR1), and number of spines. Intrathecal injection a P-Rex2-targeting RNAi lentivirus relieved BCP and reduced the expression of P-Rex2, p-Rac1, p-GluR1, and number of spines in the BCP mice. Meanwhile, P-Rex2 knockdown reversed BCP-enhanced AMPA receptor (AMPAR)-induced current in dorsal horn neurons. In summary, this study suggested that P-Rex2 regulated GluR1-containing AMPAR trafficking and spine morphology via Rac1/pGluR1 pathway is a fundamental pathogenesis of BCP. Our findings provide a better understanding of the function of P-Rex2 as a possible therapeutic target for relieving BCP.</description><subject>Animals</subject><subject>Bone cancer</subject><subject>Bone Neoplasms - complications</subject><subject>Cancer Pain</subject><subject>Chronic pain</subject><subject>Dendritic spines</subject><subject>Dorsal horn</subject><subject>Glutamate receptors</subject><subject>Glutamic acid receptors (ionotropic)</subject><subject>GTPase-Activating Proteins</subject><subject>Guanine nucleotide exchange factor</subject><subject>Guanine Nucleotide Exchange Factors - genetics</subject><subject>Hyperalgesia</subject><subject>Mice</subject><subject>Neuronal Plasticity</subject><subject>Pain perception</subject><subject>Quality of Life</subject><subject>Rac1 protein</subject><subject>RNA-mediated interference</subject><subject>Synaptic plasticity</subject><subject>Therapeutic targets</subject><subject>Tumor cells</subject><subject>α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid</subject><subject>α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors</subject><issn>1744-8069</issn><issn>1744-8069</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</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><recordid>eNp1kVlrGzEUhUVJaJzlB_SlCPqSl3G1jTTzEighSyHQENJnodWVGUvT0Uyp_31k7LpZCAiuuPru0bkcAD5hNMdYiK9YMNYg3hKCkeCMow9gtulVm-bBs_sROM55iRAViOOP4IjWqKEtwzNwc189uL8ErpwNagwpwuRhXkfVj8HAvlO51DCuoUlxHIKeRpfhmKBO0UGjonED7FWIp-DQqy67s109AT-vrx4vb6u7HzffL7_dVYZxPlaWCcUt997Wdcu59ghr6hw1iBDtam9qarG23mJUa6uZEV6gphzbGC8MoifgYqvbT7p4Nq64Up3sh7BSw1omFeTLlxh-yUX6I5umxS1qi8D5TmBIvyeXR7kK2biuU9GlKUvCCaWkrTEr6JdX6DJNQyzrSSLqhjJGGC0U3lJmSDkPzu_NYCQ3Mck3MZWZz8-32E_8y6UA8y2Q1cL9__Z9xSdT5ZtU</recordid><startdate>20220223</startdate><enddate>20220223</enddate><creator>Fu, Qiaochu</creator><creator>Huang, Xiaoxia</creator><creator>Wan, Shengjun</creator><creator>Li, Yang</creator><creator>Li, Xiaohui</creator><creator>Su, Shanchun</creator><creator>Xu, Xueqin</creator><creator>Wu, Yanqiong</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><orcidid>https://orcid.org/0000-0002-3001-0061</orcidid></search><sort><creationdate>20220223</creationdate><title>P-Rex2 mediation of synaptic plasticity contributes to bone cancer pain</title><author>Fu, Qiaochu ; Huang, Xiaoxia ; Wan, Shengjun ; Li, Yang ; Li, Xiaohui ; Su, Shanchun ; Xu, Xueqin ; Wu, Yanqiong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c466t-d47a6d6ffd55966bf01b3ee3c022be5fc53d1bdfd105bdb4c7f708708d8cf7c03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animals</topic><topic>Bone cancer</topic><topic>Bone Neoplasms - complications</topic><topic>Cancer Pain</topic><topic>Chronic pain</topic><topic>Dendritic spines</topic><topic>Dorsal horn</topic><topic>Glutamate receptors</topic><topic>Glutamic acid receptors (ionotropic)</topic><topic>GTPase-Activating Proteins</topic><topic>Guanine nucleotide exchange factor</topic><topic>Guanine Nucleotide Exchange Factors - genetics</topic><topic>Hyperalgesia</topic><topic>Mice</topic><topic>Neuronal Plasticity</topic><topic>Pain perception</topic><topic>Quality of Life</topic><topic>Rac1 protein</topic><topic>RNA-mediated interference</topic><topic>Synaptic plasticity</topic><topic>Therapeutic targets</topic><topic>Tumor cells</topic><topic>α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid</topic><topic>α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fu, Qiaochu</creatorcontrib><creatorcontrib>Huang, Xiaoxia</creatorcontrib><creatorcontrib>Wan, Shengjun</creatorcontrib><creatorcontrib>Li, Yang</creatorcontrib><creatorcontrib>Li, Xiaohui</creatorcontrib><creatorcontrib>Su, Shanchun</creatorcontrib><creatorcontrib>Xu, Xueqin</creatorcontrib><creatorcontrib>Wu, Yanqiong</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><jtitle>Molecular pain</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fu, Qiaochu</au><au>Huang, Xiaoxia</au><au>Wan, Shengjun</au><au>Li, Yang</au><au>Li, Xiaohui</au><au>Su, Shanchun</au><au>Xu, Xueqin</au><au>Wu, Yanqiong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>P-Rex2 mediation of synaptic plasticity contributes to bone cancer pain</atitle><jtitle>Molecular pain</jtitle><addtitle>Mol Pain</addtitle><date>2022-02-23</date><risdate>2022</risdate><volume>18</volume><spage>17448069221076460</spage><epage>17448069221076460</epage><pages>17448069221076460-17448069221076460</pages><issn>1744-8069</issn><eissn>1744-8069</eissn><abstract>Bone cancer pain (BCP) seriously affects the quality of life; however, due to its complex mechanism, the clinical treatment was unsatisfactory. Recent studies have showed several Rac-specific guanine nucleotide exchange factors (GEFs) that affect development and structure of neuronal processes play a vital role in the regulation of chronic pain. P-Rex2 is one of GEFs that regulate spine density, and the present study was performed to examine the effect of P-Rex2 on the development of BCP. Tumor cells implantation induced the mechanical hyperalgesia, which was accompanied by an increase in spinal protein P-Rex2, phosphorylated Rac1 (p-Rac1) and phosphorylated GluR1 (p-GluR1), and number of spines. Intrathecal injection a P-Rex2-targeting RNAi lentivirus relieved BCP and reduced the expression of P-Rex2, p-Rac1, p-GluR1, and number of spines in the BCP mice. Meanwhile, P-Rex2 knockdown reversed BCP-enhanced AMPA receptor (AMPAR)-induced current in dorsal horn neurons. In summary, this study suggested that P-Rex2 regulated GluR1-containing AMPAR trafficking and spine morphology via Rac1/pGluR1 pathway is a fundamental pathogenesis of BCP. Our findings provide a better understanding of the function of P-Rex2 as a possible therapeutic target for relieving BCP.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>35083941</pmid><doi>10.1177/17448069221076460</doi><orcidid>https://orcid.org/0000-0002-3001-0061</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Bone cancer Bone Neoplasms - complications Cancer Pain Chronic pain Dendritic spines Dorsal horn Glutamate receptors Glutamic acid receptors (ionotropic) GTPase-Activating Proteins Guanine nucleotide exchange factor Guanine Nucleotide Exchange Factors - genetics Hyperalgesia Mice Neuronal Plasticity Pain perception Quality of Life Rac1 protein RNA-mediated interference Synaptic plasticity Therapeutic targets Tumor cells α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors |
| title | P-Rex2 mediation of synaptic plasticity contributes to bone cancer pain |
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