The hypotension evoked by visceral nociception is mediated by delta opioid receptors in the periaqueductal gray

This study tested the hypothesis that the ventrolateral column of the midbrain periaqueductal gray (vlPAG) region mediates the hypotension and bradycardia evoked by visceral nociception. To test this, the local anesthetic lidocaine (2%; 0.5 μl) was microinjected into the vlPAG of halothane-anestheti...

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Veröffentlicht in:Brain research 2004-09, Vol.1019 (1-2), p.237-245
Hauptverfasser: Cavun, Sinan, Goktalay, Gokhan, Millington, William R
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description This study tested the hypothesis that the ventrolateral column of the midbrain periaqueductal gray (vlPAG) region mediates the hypotension and bradycardia evoked by visceral nociception. To test this, the local anesthetic lidocaine (2%; 0.5 μl) was microinjected into the vlPAG of halothane-anesthetized rats bilaterally and visceral nociception was induced 2 min later by injecting 5% acetic acid (0.5 ml) intraperitoneally. Acetic acid injection caused an abrupt fall in arterial pressure (−12.2±2.1 mm Hg) and heart rate (−37±93 bpm) lasting approximately 15 min. Lidocaine injection into the vlPAG prevented the fall in arterial pressure and heart rate completely. Cobalt chloride (5 mM; 0.2 or 0.5 μl) injection into the vlPAG also prevented nociceptive hypotension but it did not affect the fall in heart rate significantly. Lidocaine pretreatment also inhibited the depressor response caused by intramuscular formalin (5%; 0.2 ml) administration, a model of deep somatic nociception, although it did not prevent the response completely. To determine if opioid receptors mediate the response, selective mu, delta or kappa opioid receptor antagonists were microinjected into the vlPAG 5 min before intraperitoneal (ip) acetic acid administration. Naltrindole, a delta receptor antagonist, inhibited the response significantly but mu and kappa antagonists were completely ineffective. Lidocaine and naltrindole had no effect when injected into the dorsolateral PAG and did not influence cardiovascular function when injected into the vlPAG of saline treated control animals. These data support the hypothesis that the vlPAG mediates the depressor response evoked by visceral nociception and indicate that delta opioid receptors participate in the response.
doi_str_mv 10.1016/j.brainres.2004.06.003
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To determine if opioid receptors mediate the response, selective mu, delta or kappa opioid receptor antagonists were microinjected into the vlPAG 5 min before intraperitoneal (ip) acetic acid administration. Naltrindole, a delta receptor antagonist, inhibited the response significantly but mu and kappa antagonists were completely ineffective. Lidocaine and naltrindole had no effect when injected into the dorsolateral PAG and did not influence cardiovascular function when injected into the vlPAG of saline treated control animals. 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To determine if opioid receptors mediate the response, selective mu, delta or kappa opioid receptor antagonists were microinjected into the vlPAG 5 min before intraperitoneal (ip) acetic acid administration. Naltrindole, a delta receptor antagonist, inhibited the response significantly but mu and kappa antagonists were completely ineffective. Lidocaine and naltrindole had no effect when injected into the dorsolateral PAG and did not influence cardiovascular function when injected into the vlPAG of saline treated control animals. These data support the hypothesis that the vlPAG mediates the depressor response evoked by visceral nociception and indicate that delta opioid receptors participate in the response.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Central cardiovascular regulation</subject><subject>Delta receptor</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Heart Rate - drug effects</subject><subject>Heart Rate - physiology</subject><subject>Hypotension - physiopathology</subject><subject>Male</subject><subject>Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration</subject><subject>Narcotic Antagonists - pharmacology</subject><subject>Opioid receptor</subject><subject>Pain</subject><subject>Pain Measurement - drug effects</subject><subject>Pain Measurement - methods</subject><subject>Periaqueductal gray</subject><subject>Periaqueductal Gray - drug effects</subject><subject>Periaqueductal Gray - physiology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Opioid, delta - antagonists &amp; inhibitors</subject><subject>Receptors, Opioid, delta - physiology</subject><subject>Vertebrates: nervous system and sense organs</subject><subject>Visceral nociception</subject><issn>0006-8993</issn><issn>1872-6240</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc2O2yAUhVHVqpOmfYURm3Zn9wKGmF2rUf-kkbqZrhGG6w6pY1wgkfL2xUqqWc4KXfFx7uEcQm4ZtAyY-rhvh2TDnDC3HKBrQbUA4gXZsH7HG8U7eEk2AKCaXmtxQ97kvK-jEBpekxsmBSgu-w2JD49IH89LLDjnEGeKp_gHPR3O9BSyw2QnOkcXHC5lvQ6ZHtAHWy6Mx6lYGpcQg6cJVyqmTMNMS9VdMAX794j-6ErV-Z3s-S15Ndop47vruSW_vn55uPve3P_89uPu833jOlClEegdAIPRe-m0Yq7javCOSe45V3bUXAyIzHoJI_MDaiXEILVH3vU4gBNb8uGiu6RYHeRiDut3psnOGI_ZKLXTIKV-FmS7nnMuZQXVBXQp5pxwNEsKB5vOhoFZOzF7878Ts3ZiQJk18S25vW44DjW7p2fXEirw_grY7Ow0Jju7kJ84BVLJfrX66cJhDe4UMJnsAs6u9lGjL8bH8JyXf2YPsFg</recordid><startdate>20040903</startdate><enddate>20040903</enddate><creator>Cavun, Sinan</creator><creator>Goktalay, Gokhan</creator><creator>Millington, William R</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</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>7TK</scope><scope>7X8</scope></search><sort><creationdate>20040903</creationdate><title>The hypotension evoked by visceral nociception is mediated by delta opioid receptors in the periaqueductal gray</title><author>Cavun, Sinan ; Goktalay, Gokhan ; Millington, William R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c406t-3edc0010fdd5c961c426bdc152d226af923bee1ad50f1dbe9633b59de248eb0c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Central cardiovascular regulation</topic><topic>Delta receptor</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Heart Rate - drug effects</topic><topic>Heart Rate - physiology</topic><topic>Hypotension - physiopathology</topic><topic>Male</topic><topic>Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration</topic><topic>Narcotic Antagonists - pharmacology</topic><topic>Opioid receptor</topic><topic>Pain</topic><topic>Pain Measurement - drug effects</topic><topic>Pain Measurement - methods</topic><topic>Periaqueductal gray</topic><topic>Periaqueductal Gray - drug effects</topic><topic>Periaqueductal Gray - physiology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, Opioid, delta - antagonists &amp; inhibitors</topic><topic>Receptors, Opioid, delta - physiology</topic><topic>Vertebrates: nervous system and sense organs</topic><topic>Visceral nociception</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cavun, Sinan</creatorcontrib><creatorcontrib>Goktalay, Gokhan</creatorcontrib><creatorcontrib>Millington, William R</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Brain research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cavun, Sinan</au><au>Goktalay, Gokhan</au><au>Millington, William R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The hypotension evoked by visceral nociception is mediated by delta opioid receptors in the periaqueductal gray</atitle><jtitle>Brain research</jtitle><addtitle>Brain Res</addtitle><date>2004-09-03</date><risdate>2004</risdate><volume>1019</volume><issue>1-2</issue><spage>237</spage><epage>245</epage><pages>237-245</pages><issn>0006-8993</issn><eissn>1872-6240</eissn><coden>BRREAP</coden><abstract>This study tested the hypothesis that the ventrolateral column of the midbrain periaqueductal gray (vlPAG) region mediates the hypotension and bradycardia evoked by visceral nociception. To test this, the local anesthetic lidocaine (2%; 0.5 μl) was microinjected into the vlPAG of halothane-anesthetized rats bilaterally and visceral nociception was induced 2 min later by injecting 5% acetic acid (0.5 ml) intraperitoneally. Acetic acid injection caused an abrupt fall in arterial pressure (−12.2±2.1 mm Hg) and heart rate (−37±93 bpm) lasting approximately 15 min. Lidocaine injection into the vlPAG prevented the fall in arterial pressure and heart rate completely. Cobalt chloride (5 mM; 0.2 or 0.5 μl) injection into the vlPAG also prevented nociceptive hypotension but it did not affect the fall in heart rate significantly. Lidocaine pretreatment also inhibited the depressor response caused by intramuscular formalin (5%; 0.2 ml) administration, a model of deep somatic nociception, although it did not prevent the response completely. To determine if opioid receptors mediate the response, selective mu, delta or kappa opioid receptor antagonists were microinjected into the vlPAG 5 min before intraperitoneal (ip) acetic acid administration. Naltrindole, a delta receptor antagonist, inhibited the response significantly but mu and kappa antagonists were completely ineffective. Lidocaine and naltrindole had no effect when injected into the dorsolateral PAG and did not influence cardiovascular function when injected into the vlPAG of saline treated control animals. These data support the hypothesis that the vlPAG mediates the depressor response evoked by visceral nociception and indicate that delta opioid receptors participate in the response.</abstract><cop>London</cop><cop>Amsterdam</cop><cop>New York, NY</cop><pub>Elsevier B.V</pub><pmid>15306258</pmid><doi>10.1016/j.brainres.2004.06.003</doi><tpages>9</tpages></addata></record>
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source MEDLINE; Elsevier ScienceDirect Journals Complete
subjects Animals
Biological and medical sciences
Central cardiovascular regulation
Delta receptor
Fundamental and applied biological sciences. Psychology
Heart Rate - drug effects
Heart Rate - physiology
Hypotension - physiopathology
Male
Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration
Narcotic Antagonists - pharmacology
Opioid receptor
Pain
Pain Measurement - drug effects
Pain Measurement - methods
Periaqueductal gray
Periaqueductal Gray - drug effects
Periaqueductal Gray - physiology
Rats
Rats, Sprague-Dawley
Receptors, Opioid, delta - antagonists & inhibitors
Receptors, Opioid, delta - physiology
Vertebrates: nervous system and sense organs
Visceral nociception
title The hypotension evoked by visceral nociception is mediated by delta opioid receptors in the periaqueductal gray
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