Two TRPV1 receptor antagonists are effective in two different experimental models of migraine
Background The capsaicin and heat responsive ion channel TRPV1 is expressed on trigeminal nociceptive neurons and has been implicated in the pathophysiology of migraine attacks. Here we investigate the efficacy of two TRPV1 channel antagonists in blocking trigeminal activation using two in vivo mode...
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| Veröffentlicht in: | Journal of headache and pain 2015-06, Vol.16 (1), p.57-57, Article 57 |
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| creator | Meents, Jannis E Hoffmann, Jan Chaplan, Sandra R Neeb, Lars Schuh-Hofer, Sigrid Wickenden, Alan Reuter, Uwe |
| description | Background
The capsaicin and heat responsive ion channel TRPV1 is expressed on trigeminal nociceptive neurons and has been implicated in the pathophysiology of migraine attacks. Here we investigate the efficacy of two TRPV1 channel antagonists in blocking trigeminal activation using two
in vivo
models of migraine.
Methods
Male Sprague–Dawley rats were used to study the effects of the TRPV1 antagonists JNJ-38893777 and JNJ-17203212 on trigeminal activation. Expression of the immediate early gene
c-fos
was measured following intracisternal application of inflammatory soup. In a second model, CGRP release into the external jugular vein was determined following injection of capsaicin into the carotid artery.
Results
Inflammatory up-regulation of
c-fos
in the trigeminal brain stem complex was dose-dependently and significantly reduced by both TRPV1 antagonists. Capsaicin-induced CGRP release was attenuated by JNJ-38893777 only in higher dosage. JNJ-17203212 was effective in all doses and fully abolished CGRP release in a time and dose-dependent manner.
Conclusion
Our results describe two TRPV1 antagonists that are effective in two
in vivo
models of migraine. These results suggest that TRPV1 may play a role in the pathophysiological mechanisms, which are relevant to migraine. |
| doi_str_mv | 10.1186/s10194-015-0539-z |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4491068</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1805495650</sourcerecordid><originalsourceid>FETCH-LOGICAL-c639t-cfaf057e71b5b4e07a9d831191e190061de666db0e29323d61dcd9679a6d0163</originalsourceid><addsrcrecordid>eNqFkU9r3DAQxUVJadJtP0AvRZBLLm5nLFu2LoEQkrYQaClLb0VorfFWwZa2kjf_Pn217HZJA6EnDZrfvHnSY-wdwgfEVn5MCKiqArAuoBaqeHjBjhBLVZSiaQ72tVSH7HVK1wAliLZ-xQ5LiaAqIY_Yz_lt4PPv334gj9TRagqRGz-ZZfAuTYmbSJz6nrrJ3RB3nk-Zty7fRPITp7sVRTfm0gx8DJaGxEPPR7eMxnl6w172Zkj0dnfO2PzyYn7-ubj6-unL-dlV0UmhpqLrTQ91Qw0u6kVF0BhlW4GokFABSLQkpbQLoFKJUth80VklG2WkBZRixk63sqv1YiTbZTvRDHqVnZl4r4Nx-t-Od7_0MtzoqlIIss0CJzuBGH6vKU16dKmjYTCewjppbKGuVC1r-D8qFcrsGaqMHj9Br8M6-vwRG0o0ANhuduOW6mJIKVK_942gNzHrbcw6x6w3MeuHPPP-8YP3E39zzUC5BVJu-SXFR6ufVf0Dra6zwg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1693700188</pqid></control><display><type>article</type><title>Two TRPV1 receptor antagonists are effective in two different experimental models of migraine</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Springer Nature OA/Free Journals</source><source>PubMed Central Open Access</source><creator>Meents, Jannis E ; Hoffmann, Jan ; Chaplan, Sandra R ; Neeb, Lars ; Schuh-Hofer, Sigrid ; Wickenden, Alan ; Reuter, Uwe</creator><creatorcontrib>Meents, Jannis E ; Hoffmann, Jan ; Chaplan, Sandra R ; Neeb, Lars ; Schuh-Hofer, Sigrid ; Wickenden, Alan ; Reuter, Uwe</creatorcontrib><description>Background
The capsaicin and heat responsive ion channel TRPV1 is expressed on trigeminal nociceptive neurons and has been implicated in the pathophysiology of migraine attacks. Here we investigate the efficacy of two TRPV1 channel antagonists in blocking trigeminal activation using two
in vivo
models of migraine.
Methods
Male Sprague–Dawley rats were used to study the effects of the TRPV1 antagonists JNJ-38893777 and JNJ-17203212 on trigeminal activation. Expression of the immediate early gene
c-fos
was measured following intracisternal application of inflammatory soup. In a second model, CGRP release into the external jugular vein was determined following injection of capsaicin into the carotid artery.
Results
Inflammatory up-regulation of
c-fos
in the trigeminal brain stem complex was dose-dependently and significantly reduced by both TRPV1 antagonists. Capsaicin-induced CGRP release was attenuated by JNJ-38893777 only in higher dosage. JNJ-17203212 was effective in all doses and fully abolished CGRP release in a time and dose-dependent manner.
Conclusion
Our results describe two TRPV1 antagonists that are effective in two
in vivo
models of migraine. These results suggest that TRPV1 may play a role in the pathophysiological mechanisms, which are relevant to migraine.</description><identifier>ISSN: 1129-2369</identifier><identifier>EISSN: 1129-2377</identifier><identifier>DOI: 10.1186/s10194-015-0539-z</identifier><identifier>PMID: 26109436</identifier><identifier>CODEN: JHPOAT</identifier><language>eng</language><publisher>Milan: Springer Milan</publisher><subject>Aminopyridines - pharmacology ; Aminopyridines - therapeutic use ; Animals ; Antagonist drugs ; Capsaicin - toxicity ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Genes, fos - drug effects ; Internal Medicine ; Male ; Medicine ; Medicine & Public Health ; Migraine ; Migraine Disorders - chemically induced ; Migraine Disorders - drug therapy ; Migraine Disorders - metabolism ; Neurology ; Pain Medicine ; Piperazines - pharmacology ; Piperazines - therapeutic use ; Rats ; Rats, Sprague-Dawley ; Research Article ; Rodents ; Treatment Outcome ; TRPV Cation Channels - antagonists & inhibitors ; Up-Regulation - drug effects</subject><ispartof>Journal of headache and pain, 2015-06, Vol.16 (1), p.57-57, Article 57</ispartof><rights>Meents et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.</rights><rights>The Author(s) 2015</rights><rights>Meents et al. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c639t-cfaf057e71b5b4e07a9d831191e190061de666db0e29323d61dcd9679a6d0163</citedby><cites>FETCH-LOGICAL-c639t-cfaf057e71b5b4e07a9d831191e190061de666db0e29323d61dcd9679a6d0163</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/PMC4491068/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4491068/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,41464,42165,42533,51294,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26109436$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Meents, Jannis E</creatorcontrib><creatorcontrib>Hoffmann, Jan</creatorcontrib><creatorcontrib>Chaplan, Sandra R</creatorcontrib><creatorcontrib>Neeb, Lars</creatorcontrib><creatorcontrib>Schuh-Hofer, Sigrid</creatorcontrib><creatorcontrib>Wickenden, Alan</creatorcontrib><creatorcontrib>Reuter, Uwe</creatorcontrib><title>Two TRPV1 receptor antagonists are effective in two different experimental models of migraine</title><title>Journal of headache and pain</title><addtitle>J Headache Pain</addtitle><addtitle>J Headache Pain</addtitle><description>Background
The capsaicin and heat responsive ion channel TRPV1 is expressed on trigeminal nociceptive neurons and has been implicated in the pathophysiology of migraine attacks. Here we investigate the efficacy of two TRPV1 channel antagonists in blocking trigeminal activation using two
in vivo
models of migraine.
Methods
Male Sprague–Dawley rats were used to study the effects of the TRPV1 antagonists JNJ-38893777 and JNJ-17203212 on trigeminal activation. Expression of the immediate early gene
c-fos
was measured following intracisternal application of inflammatory soup. In a second model, CGRP release into the external jugular vein was determined following injection of capsaicin into the carotid artery.
Results
Inflammatory up-regulation of
c-fos
in the trigeminal brain stem complex was dose-dependently and significantly reduced by both TRPV1 antagonists. Capsaicin-induced CGRP release was attenuated by JNJ-38893777 only in higher dosage. JNJ-17203212 was effective in all doses and fully abolished CGRP release in a time and dose-dependent manner.
Conclusion
Our results describe two TRPV1 antagonists that are effective in two
in vivo
models of migraine. These results suggest that TRPV1 may play a role in the pathophysiological mechanisms, which are relevant to migraine.</description><subject>Aminopyridines - pharmacology</subject><subject>Aminopyridines - therapeutic use</subject><subject>Animals</subject><subject>Antagonist drugs</subject><subject>Capsaicin - toxicity</subject><subject>Disease Models, Animal</subject><subject>Dose-Response Relationship, Drug</subject><subject>Genes, fos - drug effects</subject><subject>Internal Medicine</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Migraine</subject><subject>Migraine Disorders - chemically induced</subject><subject>Migraine Disorders - drug therapy</subject><subject>Migraine Disorders - metabolism</subject><subject>Neurology</subject><subject>Pain Medicine</subject><subject>Piperazines - pharmacology</subject><subject>Piperazines - therapeutic use</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Research Article</subject><subject>Rodents</subject><subject>Treatment Outcome</subject><subject>TRPV Cation Channels - antagonists & inhibitors</subject><subject>Up-Regulation - drug effects</subject><issn>1129-2369</issn><issn>1129-2377</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkU9r3DAQxUVJadJtP0AvRZBLLm5nLFu2LoEQkrYQaClLb0VorfFWwZa2kjf_Pn217HZJA6EnDZrfvHnSY-wdwgfEVn5MCKiqArAuoBaqeHjBjhBLVZSiaQ72tVSH7HVK1wAliLZ-xQ5LiaAqIY_Yz_lt4PPv334gj9TRagqRGz-ZZfAuTYmbSJz6nrrJ3RB3nk-Zty7fRPITp7sVRTfm0gx8DJaGxEPPR7eMxnl6w172Zkj0dnfO2PzyYn7-ubj6-unL-dlV0UmhpqLrTQ91Qw0u6kVF0BhlW4GokFABSLQkpbQLoFKJUth80VklG2WkBZRixk63sqv1YiTbZTvRDHqVnZl4r4Nx-t-Od7_0MtzoqlIIss0CJzuBGH6vKU16dKmjYTCewjppbKGuVC1r-D8qFcrsGaqMHj9Br8M6-vwRG0o0ANhuduOW6mJIKVK_942gNzHrbcw6x6w3MeuHPPP-8YP3E39zzUC5BVJu-SXFR6ufVf0Dra6zwg</recordid><startdate>20150624</startdate><enddate>20150624</enddate><creator>Meents, Jannis E</creator><creator>Hoffmann, Jan</creator><creator>Chaplan, Sandra R</creator><creator>Neeb, Lars</creator><creator>Schuh-Hofer, Sigrid</creator><creator>Wickenden, Alan</creator><creator>Reuter, Uwe</creator><general>Springer Milan</general><general>Springer Nature B.V</general><scope>C6C</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>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</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>GNUQQ</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>NAPCQ</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150624</creationdate><title>Two TRPV1 receptor antagonists are effective in two different experimental models of migraine</title><author>Meents, Jannis E ; Hoffmann, Jan ; Chaplan, Sandra R ; Neeb, Lars ; Schuh-Hofer, Sigrid ; Wickenden, Alan ; Reuter, Uwe</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c639t-cfaf057e71b5b4e07a9d831191e190061de666db0e29323d61dcd9679a6d0163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Aminopyridines - pharmacology</topic><topic>Aminopyridines - therapeutic use</topic><topic>Animals</topic><topic>Antagonist drugs</topic><topic>Capsaicin - toxicity</topic><topic>Disease Models, Animal</topic><topic>Dose-Response Relationship, Drug</topic><topic>Genes, fos - drug effects</topic><topic>Internal Medicine</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Migraine</topic><topic>Migraine Disorders - chemically induced</topic><topic>Migraine Disorders - drug therapy</topic><topic>Migraine Disorders - metabolism</topic><topic>Neurology</topic><topic>Pain Medicine</topic><topic>Piperazines - pharmacology</topic><topic>Piperazines - therapeutic use</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Research Article</topic><topic>Rodents</topic><topic>Treatment Outcome</topic><topic>TRPV Cation Channels - antagonists & inhibitors</topic><topic>Up-Regulation - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Meents, Jannis E</creatorcontrib><creatorcontrib>Hoffmann, Jan</creatorcontrib><creatorcontrib>Chaplan, Sandra R</creatorcontrib><creatorcontrib>Neeb, Lars</creatorcontrib><creatorcontrib>Schuh-Hofer, Sigrid</creatorcontrib><creatorcontrib>Wickenden, Alan</creatorcontrib><creatorcontrib>Reuter, Uwe</creatorcontrib><collection>Springer Nature OA/Free Journals</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>Nursing & Allied Health Database</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>Psychology Database (Alumni)</collection><collection>ProQuest Pharma 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>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 Central Student</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>Nursing & Allied Health Premium</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>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of headache and pain</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Meents, Jannis E</au><au>Hoffmann, Jan</au><au>Chaplan, Sandra R</au><au>Neeb, Lars</au><au>Schuh-Hofer, Sigrid</au><au>Wickenden, Alan</au><au>Reuter, Uwe</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Two TRPV1 receptor antagonists are effective in two different experimental models of migraine</atitle><jtitle>Journal of headache and pain</jtitle><stitle>J Headache Pain</stitle><addtitle>J Headache Pain</addtitle><date>2015-06-24</date><risdate>2015</risdate><volume>16</volume><issue>1</issue><spage>57</spage><epage>57</epage><pages>57-57</pages><artnum>57</artnum><issn>1129-2369</issn><eissn>1129-2377</eissn><coden>JHPOAT</coden><abstract>Background
The capsaicin and heat responsive ion channel TRPV1 is expressed on trigeminal nociceptive neurons and has been implicated in the pathophysiology of migraine attacks. Here we investigate the efficacy of two TRPV1 channel antagonists in blocking trigeminal activation using two
in vivo
models of migraine.
Methods
Male Sprague–Dawley rats were used to study the effects of the TRPV1 antagonists JNJ-38893777 and JNJ-17203212 on trigeminal activation. Expression of the immediate early gene
c-fos
was measured following intracisternal application of inflammatory soup. In a second model, CGRP release into the external jugular vein was determined following injection of capsaicin into the carotid artery.
Results
Inflammatory up-regulation of
c-fos
in the trigeminal brain stem complex was dose-dependently and significantly reduced by both TRPV1 antagonists. Capsaicin-induced CGRP release was attenuated by JNJ-38893777 only in higher dosage. JNJ-17203212 was effective in all doses and fully abolished CGRP release in a time and dose-dependent manner.
Conclusion
Our results describe two TRPV1 antagonists that are effective in two
in vivo
models of migraine. These results suggest that TRPV1 may play a role in the pathophysiological mechanisms, which are relevant to migraine.</abstract><cop>Milan</cop><pub>Springer Milan</pub><pmid>26109436</pmid><doi>10.1186/s10194-015-0539-z</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Springer Nature - Complete Springer Journals; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Springer Nature OA/Free Journals; PubMed Central Open Access |
| subjects | Aminopyridines - pharmacology Aminopyridines - therapeutic use Animals Antagonist drugs Capsaicin - toxicity Disease Models, Animal Dose-Response Relationship, Drug Genes, fos - drug effects Internal Medicine Male Medicine Medicine & Public Health Migraine Migraine Disorders - chemically induced Migraine Disorders - drug therapy Migraine Disorders - metabolism Neurology Pain Medicine Piperazines - pharmacology Piperazines - therapeutic use Rats Rats, Sprague-Dawley Research Article Rodents Treatment Outcome TRPV Cation Channels - antagonists & inhibitors Up-Regulation - drug effects |
| title | Two TRPV1 receptor antagonists are effective in two different experimental models of migraine |
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