Hypothalamospinal oxytocinergic antinociception is mediated by GABAergic and opiate neurons that reduce A-delta and C fiber primary afferent excitation of spinal cord cells
Abstract Recent results implicate a new original mechanism involving oxytocin (OT), as a mediator via descending fibers of the paraventricular hypothalamic nucleus (PVN), in antinociception and analgesia. In rats electrical stimulation of the PVN or topical application of OT selectively inhibits A-d...
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| Veröffentlicht in: | Brain research 2009-01, Vol.1247, p.38-49 |
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| creator | Condés-Lara, Miguel Rojas-Piloni, Gerardo Martínez-Lorenzana, Guadalupe López-Hidalgo, Mónica Rodríguez-Jiménez, Javier |
| description | Abstract Recent results implicate a new original mechanism involving oxytocin (OT), as a mediator via descending fibers of the paraventricular hypothalamic nucleus (PVN), in antinociception and analgesia. In rats electrical stimulation of the PVN or topical application of OT selectively inhibits A-delta and C fiber responses in superficial dorsal horn neurons, and this inhibition is reversed by a selective OT antagonist. However, little is known about the mechanisms and the spinal elements participating in this phenomenon. Here we show that topical application of bicuculline blocks the effects produced by PVN electrical stimulation or OT application. PVN electrical stimulation also activates a subpopulation of neurons in lamina II. These PVN-On cells are responsible for the amplification of local GABAergic inhibition. This result reinforces the suggestion that a supraspinal descending control of pain processing uses a specific neuronal pathway in the spinal cord in order to produce antinociception involving a GABAergic interneuron. Moreover, the topical administration of naloxone or a μ-opiate receptor antagonist β-funaltrexamine only partially blocks the inhibitory effects produced by OT application or PVN electrical stimulation. Thus, this OT mechanism only involves opiate participation to a minor extent. The OT-specific, endogenous descending pathway represents an interesting mechanism to resolve chronic pain problems in special the neuropathic pain. |
| doi_str_mv | 10.1016/j.brainres.2008.10.030 |
| format | Article |
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In rats electrical stimulation of the PVN or topical application of OT selectively inhibits A-delta and C fiber responses in superficial dorsal horn neurons, and this inhibition is reversed by a selective OT antagonist. However, little is known about the mechanisms and the spinal elements participating in this phenomenon. Here we show that topical application of bicuculline blocks the effects produced by PVN electrical stimulation or OT application. PVN electrical stimulation also activates a subpopulation of neurons in lamina II. These PVN-On cells are responsible for the amplification of local GABAergic inhibition. This result reinforces the suggestion that a supraspinal descending control of pain processing uses a specific neuronal pathway in the spinal cord in order to produce antinociception involving a GABAergic interneuron. Moreover, the topical administration of naloxone or a μ-opiate receptor antagonist β-funaltrexamine only partially blocks the inhibitory effects produced by OT application or PVN electrical stimulation. Thus, this OT mechanism only involves opiate participation to a minor extent. The OT-specific, endogenous descending pathway represents an interesting mechanism to resolve chronic pain problems in special the neuropathic pain.</description><identifier>ISSN: 0006-8993</identifier><identifier>EISSN: 1872-6240</identifier><identifier>DOI: 10.1016/j.brainres.2008.10.030</identifier><identifier>PMID: 18996098</identifier><identifier>CODEN: BRREAP</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Analgesia ; Animals ; Bicuculline - pharmacology ; Biological and medical sciences ; Efferent Pathways - cytology ; Efferent Pathways - metabolism ; Electric Stimulation ; Fundamental and applied biological sciences. Psychology ; GABA Antagonists - pharmacology ; gamma-Aminobutyric Acid - metabolism ; Hypothalamus - cytology ; Hypothalamus - metabolism ; Narcotic Antagonists - pharmacology ; Nerve Fibers, Myelinated - drug effects ; Nerve Fibers, Myelinated - metabolism ; Nerve Fibers, Myelinated - ultrastructure ; Nerve Fibers, Unmyelinated - drug effects ; Nerve Fibers, Unmyelinated - metabolism ; Nerve Fibers, Unmyelinated - ultrastructure ; Neural Inhibition - drug effects ; Neural Inhibition - physiology ; Neurology ; Neurons - cytology ; Neurons - metabolism ; Nociceptors - cytology ; Nociceptors - drug effects ; Nociceptors - metabolism ; Opiate ; Opioid Peptides - metabolism ; Oxytocin - metabolism ; Oxytocin - pharmacology ; Pain - metabolism ; Pain - physiopathology ; Posterior Horn Cells - cytology ; Posterior Horn Cells - drug effects ; Posterior Horn Cells - metabolism ; Presynaptic inhibition ; Rat Endogenous descending control ; Rats ; Rats, Wistar ; Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors ; Spinal Cord - cytology ; Spinal Cord - drug effects ; Spinal Cord - metabolism ; Spinal Nerve Roots - cytology ; Spinal Nerve Roots - drug effects ; Spinal Nerve Roots - metabolism ; Synaptic Transmission - drug effects ; Synaptic Transmission - physiology ; Vertebrates: nervous system and sense organs</subject><ispartof>Brain research, 2009-01, Vol.1247, p.38-49</ispartof><rights>Elsevier B.V.</rights><rights>2008 Elsevier B.V.</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c482t-1275d01da16d399b7dd0a11851854a3c90119235f8136485318c78fcf10bd51d3</citedby><cites>FETCH-LOGICAL-c482t-1275d01da16d399b7dd0a11851854a3c90119235f8136485318c78fcf10bd51d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.brainres.2008.10.030$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21093239$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18996098$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Condés-Lara, Miguel</creatorcontrib><creatorcontrib>Rojas-Piloni, Gerardo</creatorcontrib><creatorcontrib>Martínez-Lorenzana, Guadalupe</creatorcontrib><creatorcontrib>López-Hidalgo, Mónica</creatorcontrib><creatorcontrib>Rodríguez-Jiménez, Javier</creatorcontrib><title>Hypothalamospinal oxytocinergic antinociception is mediated by GABAergic and opiate neurons that reduce A-delta and C fiber primary afferent excitation of spinal cord cells</title><title>Brain research</title><addtitle>Brain Res</addtitle><description>Abstract Recent results implicate a new original mechanism involving oxytocin (OT), as a mediator via descending fibers of the paraventricular hypothalamic nucleus (PVN), in antinociception and analgesia. In rats electrical stimulation of the PVN or topical application of OT selectively inhibits A-delta and C fiber responses in superficial dorsal horn neurons, and this inhibition is reversed by a selective OT antagonist. However, little is known about the mechanisms and the spinal elements participating in this phenomenon. Here we show that topical application of bicuculline blocks the effects produced by PVN electrical stimulation or OT application. PVN electrical stimulation also activates a subpopulation of neurons in lamina II. These PVN-On cells are responsible for the amplification of local GABAergic inhibition. This result reinforces the suggestion that a supraspinal descending control of pain processing uses a specific neuronal pathway in the spinal cord in order to produce antinociception involving a GABAergic interneuron. Moreover, the topical administration of naloxone or a μ-opiate receptor antagonist β-funaltrexamine only partially blocks the inhibitory effects produced by OT application or PVN electrical stimulation. Thus, this OT mechanism only involves opiate participation to a minor extent. The OT-specific, endogenous descending pathway represents an interesting mechanism to resolve chronic pain problems in special the neuropathic pain.</description><subject>Analgesia</subject><subject>Animals</subject><subject>Bicuculline - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Efferent Pathways - cytology</subject><subject>Efferent Pathways - metabolism</subject><subject>Electric Stimulation</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>GABA Antagonists - pharmacology</subject><subject>gamma-Aminobutyric Acid - metabolism</subject><subject>Hypothalamus - cytology</subject><subject>Hypothalamus - metabolism</subject><subject>Narcotic Antagonists - pharmacology</subject><subject>Nerve Fibers, Myelinated - drug effects</subject><subject>Nerve Fibers, Myelinated - metabolism</subject><subject>Nerve Fibers, Myelinated - ultrastructure</subject><subject>Nerve Fibers, Unmyelinated - drug effects</subject><subject>Nerve Fibers, Unmyelinated - metabolism</subject><subject>Nerve Fibers, Unmyelinated - ultrastructure</subject><subject>Neural Inhibition - drug effects</subject><subject>Neural Inhibition - physiology</subject><subject>Neurology</subject><subject>Neurons - cytology</subject><subject>Neurons - metabolism</subject><subject>Nociceptors - cytology</subject><subject>Nociceptors - drug effects</subject><subject>Nociceptors - metabolism</subject><subject>Opiate</subject><subject>Opioid Peptides - metabolism</subject><subject>Oxytocin - metabolism</subject><subject>Oxytocin - pharmacology</subject><subject>Pain - metabolism</subject><subject>Pain - physiopathology</subject><subject>Posterior Horn Cells - cytology</subject><subject>Posterior Horn Cells - drug effects</subject><subject>Posterior Horn Cells - metabolism</subject><subject>Presynaptic inhibition</subject><subject>Rat Endogenous descending control</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors</subject><subject>Spinal Cord - cytology</subject><subject>Spinal Cord - drug effects</subject><subject>Spinal Cord - metabolism</subject><subject>Spinal Nerve Roots - cytology</subject><subject>Spinal Nerve Roots - drug effects</subject><subject>Spinal Nerve Roots - metabolism</subject><subject>Synaptic Transmission - drug effects</subject><subject>Synaptic Transmission - physiology</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0006-8993</issn><issn>1872-6240</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks1u1DAQxyMEoqXwCpUvcMsytjeOc0EsK2iRKnEAzpZjT8BL1l5sB3XfiYfE6aYgcalkyZrxbz48_6mqSworClS83q36qJ2PmFYMQBbnCjg8qs6pbFkt2BoeV-cAIGrZdfysepbSrpicd_C0OqPFKaCT59Xv6-Mh5O961PuQDs7rkYTbYw7GeYzfnCHaZ-eLafCQXfDEJbJH63RGS_ojudq829yDloTD_EA8TjH4REreTCLaySDZ1BbHrO-wLRlcj5EcotvreCR6GDCizwRvjcv6rk4YyNKPCdESg-OYnldPBj0mfLHcF9XXD--_bK_rm09XH7ebm9qsJcs1ZW1jgVpNheVd17fWgqZUNuWsNTcdUNox3gyScrGWDafStHIwA4XeNtTyi-rVKe8hhp8Tpqz2Ls0daI9hSkqIlrdUdA-CDJiQnZAFFCfQxJBSxEEtf1cU1Cyo2ql7QdUs6OwvgpbAy6XC1Je5_wtbFCzAywXQyehxiNobl_5yjELHGZ9bfXvisAzul8OoknHoTdEyosnKBvdwL2_-S2FG512p-gOPmHZhikWvpKhKTIH6PK_fvH0ggTXAKf8DRaLZeQ</recordid><startdate>20090109</startdate><enddate>20090109</enddate><creator>Condés-Lara, Miguel</creator><creator>Rojas-Piloni, Gerardo</creator><creator>Martínez-Lorenzana, Guadalupe</creator><creator>López-Hidalgo, Mónica</creator><creator>Rodríguez-Jiménez, Javier</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>20090109</creationdate><title>Hypothalamospinal oxytocinergic antinociception is mediated by GABAergic and opiate neurons that reduce A-delta and C fiber primary afferent excitation of spinal cord cells</title><author>Condés-Lara, Miguel ; Rojas-Piloni, Gerardo ; Martínez-Lorenzana, Guadalupe ; López-Hidalgo, Mónica ; Rodríguez-Jiménez, Javier</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c482t-1275d01da16d399b7dd0a11851854a3c90119235f8136485318c78fcf10bd51d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Analgesia</topic><topic>Animals</topic><topic>Bicuculline - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Efferent Pathways - cytology</topic><topic>Efferent Pathways - metabolism</topic><topic>Electric Stimulation</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>GABA Antagonists - pharmacology</topic><topic>gamma-Aminobutyric Acid - metabolism</topic><topic>Hypothalamus - cytology</topic><topic>Hypothalamus - metabolism</topic><topic>Narcotic Antagonists - pharmacology</topic><topic>Nerve Fibers, Myelinated - drug effects</topic><topic>Nerve Fibers, Myelinated - metabolism</topic><topic>Nerve Fibers, Myelinated - ultrastructure</topic><topic>Nerve Fibers, Unmyelinated - drug effects</topic><topic>Nerve Fibers, Unmyelinated - metabolism</topic><topic>Nerve Fibers, Unmyelinated - ultrastructure</topic><topic>Neural Inhibition - drug effects</topic><topic>Neural Inhibition - physiology</topic><topic>Neurology</topic><topic>Neurons - cytology</topic><topic>Neurons - metabolism</topic><topic>Nociceptors - cytology</topic><topic>Nociceptors - drug effects</topic><topic>Nociceptors - metabolism</topic><topic>Opiate</topic><topic>Opioid Peptides - metabolism</topic><topic>Oxytocin - metabolism</topic><topic>Oxytocin - pharmacology</topic><topic>Pain - metabolism</topic><topic>Pain - physiopathology</topic><topic>Posterior Horn Cells - cytology</topic><topic>Posterior Horn Cells - drug effects</topic><topic>Posterior Horn Cells - metabolism</topic><topic>Presynaptic inhibition</topic><topic>Rat Endogenous descending control</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors</topic><topic>Spinal Cord - cytology</topic><topic>Spinal Cord - drug effects</topic><topic>Spinal Cord - metabolism</topic><topic>Spinal Nerve Roots - cytology</topic><topic>Spinal Nerve Roots - drug effects</topic><topic>Spinal Nerve Roots - metabolism</topic><topic>Synaptic Transmission - drug effects</topic><topic>Synaptic Transmission - physiology</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Condés-Lara, Miguel</creatorcontrib><creatorcontrib>Rojas-Piloni, Gerardo</creatorcontrib><creatorcontrib>Martínez-Lorenzana, Guadalupe</creatorcontrib><creatorcontrib>López-Hidalgo, Mónica</creatorcontrib><creatorcontrib>Rodríguez-Jiménez, Javier</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>Condés-Lara, Miguel</au><au>Rojas-Piloni, Gerardo</au><au>Martínez-Lorenzana, Guadalupe</au><au>López-Hidalgo, Mónica</au><au>Rodríguez-Jiménez, Javier</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hypothalamospinal oxytocinergic antinociception is mediated by GABAergic and opiate neurons that reduce A-delta and C fiber primary afferent excitation of spinal cord cells</atitle><jtitle>Brain research</jtitle><addtitle>Brain Res</addtitle><date>2009-01-09</date><risdate>2009</risdate><volume>1247</volume><spage>38</spage><epage>49</epage><pages>38-49</pages><issn>0006-8993</issn><eissn>1872-6240</eissn><coden>BRREAP</coden><abstract>Abstract Recent results implicate a new original mechanism involving oxytocin (OT), as a mediator via descending fibers of the paraventricular hypothalamic nucleus (PVN), in antinociception and analgesia. In rats electrical stimulation of the PVN or topical application of OT selectively inhibits A-delta and C fiber responses in superficial dorsal horn neurons, and this inhibition is reversed by a selective OT antagonist. However, little is known about the mechanisms and the spinal elements participating in this phenomenon. Here we show that topical application of bicuculline blocks the effects produced by PVN electrical stimulation or OT application. PVN electrical stimulation also activates a subpopulation of neurons in lamina II. These PVN-On cells are responsible for the amplification of local GABAergic inhibition. This result reinforces the suggestion that a supraspinal descending control of pain processing uses a specific neuronal pathway in the spinal cord in order to produce antinociception involving a GABAergic interneuron. Moreover, the topical administration of naloxone or a μ-opiate receptor antagonist β-funaltrexamine only partially blocks the inhibitory effects produced by OT application or PVN electrical stimulation. Thus, this OT mechanism only involves opiate participation to a minor extent. The OT-specific, endogenous descending pathway represents an interesting mechanism to resolve chronic pain problems in special the neuropathic pain.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>18996098</pmid><doi>10.1016/j.brainres.2008.10.030</doi><tpages>12</tpages></addata></record> |
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| subjects | Analgesia Animals Bicuculline - pharmacology Biological and medical sciences Efferent Pathways - cytology Efferent Pathways - metabolism Electric Stimulation Fundamental and applied biological sciences. Psychology GABA Antagonists - pharmacology gamma-Aminobutyric Acid - metabolism Hypothalamus - cytology Hypothalamus - metabolism Narcotic Antagonists - pharmacology Nerve Fibers, Myelinated - drug effects Nerve Fibers, Myelinated - metabolism Nerve Fibers, Myelinated - ultrastructure Nerve Fibers, Unmyelinated - drug effects Nerve Fibers, Unmyelinated - metabolism Nerve Fibers, Unmyelinated - ultrastructure Neural Inhibition - drug effects Neural Inhibition - physiology Neurology Neurons - cytology Neurons - metabolism Nociceptors - cytology Nociceptors - drug effects Nociceptors - metabolism Opiate Opioid Peptides - metabolism Oxytocin - metabolism Oxytocin - pharmacology Pain - metabolism Pain - physiopathology Posterior Horn Cells - cytology Posterior Horn Cells - drug effects Posterior Horn Cells - metabolism Presynaptic inhibition Rat Endogenous descending control Rats Rats, Wistar Somesthesis and somesthetic pathways (proprioception, exteroception, nociception) interoception electrolocation. Sensory receptors Spinal Cord - cytology Spinal Cord - drug effects Spinal Cord - metabolism Spinal Nerve Roots - cytology Spinal Nerve Roots - drug effects Spinal Nerve Roots - metabolism Synaptic Transmission - drug effects Synaptic Transmission - physiology Vertebrates: nervous system and sense organs |
| title | Hypothalamospinal oxytocinergic antinociception is mediated by GABAergic and opiate neurons that reduce A-delta and C fiber primary afferent excitation of spinal cord cells |
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