Heat generates oxidized linoleic acid metabolites that activate TRPV1 and produce pain in rodents
The transient receptor potential vanilloid 1 (TRPV1) channel is the principal detector of noxious heat in the peripheral nervous system. TRPV1 is expressed in many nociceptors and is involved in heat-induced hyperalgesia and thermoregulation. The precise mechanism or mechanisms mediating the thermal...
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| Veröffentlicht in: | The Journal of clinical investigation 2010-05, Vol.120 (5), p.1617-1626 |
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| creator | Patwardhan, Amol M Akopian, Armen N Ruparel, Nikita B Diogenes, Anibal Weintraub, Susan T Uhlson, Charis Murphy, Robert C Hargreaves, Kenneth M |
| description | The transient receptor potential vanilloid 1 (TRPV1) channel is the principal detector of noxious heat in the peripheral nervous system. TRPV1 is expressed in many nociceptors and is involved in heat-induced hyperalgesia and thermoregulation. The precise mechanism or mechanisms mediating the thermal sensitivity of TRPV1 are unknown. Here, we have shown that the oxidized linoleic acid metabolites 9- and 13-hydroxyoctadecadienoic acid (9- and 13-HODE) are formed in mouse and rat skin biopsies by exposure to noxious heat. 9- and 13-HODE and their metabolites, 9- and 13-oxoODE, activated TRPV1 and therefore constitute a family of endogenous TRPV1 agonists. Moreover, blocking these substances substantially decreased the heat sensitivity of TRPV1 in rats and mice and reduced nociception. Collectively, our results indicate that HODEs contribute to the heat sensitivity of TRPV1 in rodents. Because oxidized linoleic acid metabolites are released during cell injury, these findings suggest a mechanism for integrating the hyperalgesic and proinflammatory roles of TRPV1 and linoleic acid metabolites and may provide the foundation for investigating new classes of analgesic drugs. |
| doi_str_mv | 10.1172/JCI41678 |
| format | Article |
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TRPV1 is expressed in many nociceptors and is involved in heat-induced hyperalgesia and thermoregulation. The precise mechanism or mechanisms mediating the thermal sensitivity of TRPV1 are unknown. Here, we have shown that the oxidized linoleic acid metabolites 9- and 13-hydroxyoctadecadienoic acid (9- and 13-HODE) are formed in mouse and rat skin biopsies by exposure to noxious heat. 9- and 13-HODE and their metabolites, 9- and 13-oxoODE, activated TRPV1 and therefore constitute a family of endogenous TRPV1 agonists. Moreover, blocking these substances substantially decreased the heat sensitivity of TRPV1 in rats and mice and reduced nociception. Collectively, our results indicate that HODEs contribute to the heat sensitivity of TRPV1 in rodents. Because oxidized linoleic acid metabolites are released during cell injury, these findings suggest a mechanism for integrating the hyperalgesic and proinflammatory roles of TRPV1 and linoleic acid metabolites and may provide the foundation for investigating new classes of analgesic drugs.</description><identifier>ISSN: 0021-9738</identifier><identifier>EISSN: 1558-8238</identifier><identifier>DOI: 10.1172/JCI41678</identifier><identifier>PMID: 20424317</identifier><language>eng</language><publisher>United States: American Society for Clinical Investigation</publisher><subject>Acids ; Analgesia ; Animals ; Biomedical research ; Biopsy ; Fatty Acids, Unsaturated - metabolism ; Health aspects ; Heat ; Hot Temperature ; Hyperalgesia ; Ligands ; Linoleic Acid - metabolism ; Linoleic acids ; Male ; Metabolites ; Mice ; Mice, Inbred C57BL ; Models, Biological ; Neurons ; Oxygen - chemistry ; Oxygen - metabolism ; Pain ; Rats ; Rats, Sprague-Dawley ; Temperature ; TRPV Cation Channels - metabolism ; Unsaturated fatty acids</subject><ispartof>The Journal of clinical investigation, 2010-05, Vol.120 (5), p.1617-1626</ispartof><rights>COPYRIGHT 2010 American Society for Clinical Investigation</rights><rights>Copyright American Society for Clinical Investigation May 2010</rights><rights>Copyright © 2010, American Society for Clinical Investigation</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c634t-4fe24c8b2d8727738a297f4f019dc7a1bb469919a64d4b4a7a9e9f0e5db9ae7c3</citedby><cites>FETCH-LOGICAL-c634t-4fe24c8b2d8727738a297f4f019dc7a1bb469919a64d4b4a7a9e9f0e5db9ae7c3</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/PMC2860941/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860941/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20424317$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Patwardhan, Amol M</creatorcontrib><creatorcontrib>Akopian, Armen N</creatorcontrib><creatorcontrib>Ruparel, Nikita B</creatorcontrib><creatorcontrib>Diogenes, Anibal</creatorcontrib><creatorcontrib>Weintraub, Susan T</creatorcontrib><creatorcontrib>Uhlson, Charis</creatorcontrib><creatorcontrib>Murphy, Robert C</creatorcontrib><creatorcontrib>Hargreaves, Kenneth M</creatorcontrib><title>Heat generates oxidized linoleic acid metabolites that activate TRPV1 and produce pain in rodents</title><title>The Journal of clinical investigation</title><addtitle>J Clin Invest</addtitle><description>The transient receptor potential vanilloid 1 (TRPV1) channel is the principal detector of noxious heat in the peripheral nervous system. TRPV1 is expressed in many nociceptors and is involved in heat-induced hyperalgesia and thermoregulation. The precise mechanism or mechanisms mediating the thermal sensitivity of TRPV1 are unknown. Here, we have shown that the oxidized linoleic acid metabolites 9- and 13-hydroxyoctadecadienoic acid (9- and 13-HODE) are formed in mouse and rat skin biopsies by exposure to noxious heat. 9- and 13-HODE and their metabolites, 9- and 13-oxoODE, activated TRPV1 and therefore constitute a family of endogenous TRPV1 agonists. Moreover, blocking these substances substantially decreased the heat sensitivity of TRPV1 in rats and mice and reduced nociception. Collectively, our results indicate that HODEs contribute to the heat sensitivity of TRPV1 in rodents. Because oxidized linoleic acid metabolites are released during cell injury, these findings suggest a mechanism for integrating the hyperalgesic and proinflammatory roles of TRPV1 and linoleic acid metabolites and may provide the foundation for investigating new classes of analgesic drugs.</description><subject>Acids</subject><subject>Analgesia</subject><subject>Animals</subject><subject>Biomedical research</subject><subject>Biopsy</subject><subject>Fatty Acids, Unsaturated - metabolism</subject><subject>Health aspects</subject><subject>Heat</subject><subject>Hot Temperature</subject><subject>Hyperalgesia</subject><subject>Ligands</subject><subject>Linoleic Acid - metabolism</subject><subject>Linoleic acids</subject><subject>Male</subject><subject>Metabolites</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Models, Biological</subject><subject>Neurons</subject><subject>Oxygen - chemistry</subject><subject>Oxygen - metabolism</subject><subject>Pain</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Temperature</subject><subject>TRPV Cation Channels - metabolism</subject><subject>Unsaturated fatty acids</subject><issn>0021-9738</issn><issn>1558-8238</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><recordid>eNqN0u9r1DAYB_Aiijun4F8gRcEfLzqTNG2aN8I41J0MJnPubXiaPL3L6CW3Jh3b_npz3DZ2cqA0UJp-nm9DnyfLXlNyQKlgn39MZ5zWonmSTWhVNUXDyuZpNiGE0UKKstnLXoRwQQjlvOLPsz1GOOMlFZMMjhBiPkeHA0QMub-2xt6iyXvrfI9W56CtyZcYofW9XZO4SBWgo71KFfnZ6c9zmoMz-WrwZtSYr8C6PK30iC6Gl9mzDvqAr-7u-9nvb1_PpkfF8cn32fTwuNB1yWPBO2RcNy0zjWAinRmYFB3vCJVGC6Bty2spqYSaG95yECBRdgQr00pAocv97MsmdzW2SzQ6fXuAXq0Gu4ThRnmwavuNsws191eKNTWRnKaAD3cBg78cMUS1tEFj34NDPwYlqopy1rDq37IsK16zmif59i954cfBpf-gGCGVWOcl9G6D5tCjsq7z6Xx6HakOGaeS86YUSRU71KZzvXfY2bS95Q92-HQZXFq9s-DTVkEyEa_jHMYQ1OzX6f_bk_Nt-_6RXSD0cRF8P0brXdiGHzdQDz6EAbuH5lGi1nOu7uc80TePm_0A7we7_AMGTfOw</recordid><startdate>20100501</startdate><enddate>20100501</enddate><creator>Patwardhan, Amol M</creator><creator>Akopian, Armen N</creator><creator>Ruparel, Nikita B</creator><creator>Diogenes, Anibal</creator><creator>Weintraub, Susan T</creator><creator>Uhlson, Charis</creator><creator>Murphy, Robert C</creator><creator>Hargreaves, Kenneth M</creator><general>American Society for Clinical Investigation</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>S0X</scope><scope>7X8</scope><scope>7QP</scope><scope>7TK</scope><scope>5PM</scope></search><sort><creationdate>20100501</creationdate><title>Heat generates oxidized linoleic acid metabolites that activate TRPV1 and produce pain in rodents</title><author>Patwardhan, Amol M ; Akopian, Armen N ; Ruparel, Nikita B ; Diogenes, Anibal ; Weintraub, Susan T ; Uhlson, Charis ; Murphy, Robert C ; Hargreaves, Kenneth M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c634t-4fe24c8b2d8727738a297f4f019dc7a1bb469919a64d4b4a7a9e9f0e5db9ae7c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Acids</topic><topic>Analgesia</topic><topic>Animals</topic><topic>Biomedical research</topic><topic>Biopsy</topic><topic>Fatty Acids, Unsaturated - metabolism</topic><topic>Health aspects</topic><topic>Heat</topic><topic>Hot Temperature</topic><topic>Hyperalgesia</topic><topic>Ligands</topic><topic>Linoleic Acid - metabolism</topic><topic>Linoleic acids</topic><topic>Male</topic><topic>Metabolites</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Models, Biological</topic><topic>Neurons</topic><topic>Oxygen - chemistry</topic><topic>Oxygen - metabolism</topic><topic>Pain</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Temperature</topic><topic>TRPV Cation Channels - metabolism</topic><topic>Unsaturated fatty acids</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Patwardhan, Amol M</creatorcontrib><creatorcontrib>Akopian, Armen N</creatorcontrib><creatorcontrib>Ruparel, Nikita B</creatorcontrib><creatorcontrib>Diogenes, Anibal</creatorcontrib><creatorcontrib>Weintraub, Susan T</creatorcontrib><creatorcontrib>Uhlson, Charis</creatorcontrib><creatorcontrib>Murphy, Robert C</creatorcontrib><creatorcontrib>Hargreaves, Kenneth M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</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 Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</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>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of clinical investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Patwardhan, Amol M</au><au>Akopian, Armen N</au><au>Ruparel, Nikita B</au><au>Diogenes, Anibal</au><au>Weintraub, Susan T</au><au>Uhlson, Charis</au><au>Murphy, Robert C</au><au>Hargreaves, Kenneth M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Heat generates oxidized linoleic acid metabolites that activate TRPV1 and produce pain in rodents</atitle><jtitle>The Journal of clinical investigation</jtitle><addtitle>J Clin Invest</addtitle><date>2010-05-01</date><risdate>2010</risdate><volume>120</volume><issue>5</issue><spage>1617</spage><epage>1626</epage><pages>1617-1626</pages><issn>0021-9738</issn><eissn>1558-8238</eissn><abstract>The transient receptor potential vanilloid 1 (TRPV1) channel is the principal detector of noxious heat in the peripheral nervous system. TRPV1 is expressed in many nociceptors and is involved in heat-induced hyperalgesia and thermoregulation. The precise mechanism or mechanisms mediating the thermal sensitivity of TRPV1 are unknown. Here, we have shown that the oxidized linoleic acid metabolites 9- and 13-hydroxyoctadecadienoic acid (9- and 13-HODE) are formed in mouse and rat skin biopsies by exposure to noxious heat. 9- and 13-HODE and their metabolites, 9- and 13-oxoODE, activated TRPV1 and therefore constitute a family of endogenous TRPV1 agonists. Moreover, blocking these substances substantially decreased the heat sensitivity of TRPV1 in rats and mice and reduced nociception. Collectively, our results indicate that HODEs contribute to the heat sensitivity of TRPV1 in rodents. Because oxidized linoleic acid metabolites are released during cell injury, these findings suggest a mechanism for integrating the hyperalgesic and proinflammatory roles of TRPV1 and linoleic acid metabolites and may provide the foundation for investigating new classes of analgesic drugs.</abstract><cop>United States</cop><pub>American Society for Clinical Investigation</pub><pmid>20424317</pmid><doi>10.1172/JCI41678</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Acids Analgesia Animals Biomedical research Biopsy Fatty Acids, Unsaturated - metabolism Health aspects Heat Hot Temperature Hyperalgesia Ligands Linoleic Acid - metabolism Linoleic acids Male Metabolites Mice Mice, Inbred C57BL Models, Biological Neurons Oxygen - chemistry Oxygen - metabolism Pain Rats Rats, Sprague-Dawley Temperature TRPV Cation Channels - metabolism Unsaturated fatty acids |
| title | Heat generates oxidized linoleic acid metabolites that activate TRPV1 and produce pain in rodents |
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