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P." }, "creator" : { "@language" : "en", "@value" : "Bonin, R. P." }, "description" : { "@language" : "en", "@value" : "The development of new strategies for the treatment of acute pain requires the identification of novel nonopioid receptor targets. This study explored whether delta-subunit-containing GABA(A)Rs (deltaGABA(A)Rs) in neurons of the spinal cord dorsal horn generate a tonic inhibitory conductance in vitro and whether deltaGABA(A)R activity regulates acute nociception. Whole-cell recordings revealed that deltaGABA(A)Rs generate a tonic inhibitory conductance in cultured spinal neurons and lamina II neurons in spinal cord slices. Increasing deltaGABA(A)R function by applying the deltaGABA(A)R-preferring agonist 4,5,6,7-tetrahydroisoxazolo [5,4-c]pyridine-3-ol (THIP) increased the tonic current and inhibited neuronal excitability in spinal neurons from wild-type (WT) but not delta subunit null-mutant (Gabrd(-/-)) mice. In behavioral studies, baseline deltaGABA(A)R activity did not regulate acute nociception; however, THIP administered intraperitoneally or intrathecally attenuated acute nociception in WT but not Gabrd(-/-) mice. In the formalin nociception assay, the phase 1 response was similar for WT and Gabrd(-/-) mice. In contrast, the phase 2 response, which models central sensitization, was greater in Gabrd(-/-) mice than WT. THIP administered intraperitoneally or intrathecally inhibited phase 1 responses of WT but not Gabrd(-/-) mice and had no effect on phase 2 responses of WT mice. Surprisingly, THIP reduced the enhanced phase 2 response in Gabrd(-/-) mice. Together, these results suggest that deltaGABA(A)Rs in spinal neurons play a major physiological and pharmacological role in the regulation of acute nociception and central sensitization. Spinal delta-subunit-containing GABA(A) receptors were identified with electrophysiological methods and behavioral models as novel targets for the treatment of acute pain." }, "identifier" : [ "http://www.ncbi.nlm.nih.gov/pubmed/21396779", "http://olympias.lib.uoi.gr/jspui/handle/123456789/7819" ], "language" : "eng", "source" : { "@language" : "en", "@value" : "Pain" }, "subject" : [ { "@language" : "en", "@value" : "Action Potentials/drug effects/genetics" }, { "@id" : "http://semantics.gr/authorities/EKT-voc-classifier/786006816" }, { "@id" : "http://semantics.gr/authorities/EKT-voc-classifier/2093906231" } ], "title" : { "@language" : "en", "@value" : "Pharmacological enhancement of delta-subunit-containing GABA(A) receptors that generate a tonic inhibitory conductance in spinal neurons attenuates acute nociception in mice" }, "created" : "2011" } ], "@context" : { "subject" : { "@id" : "http://purl.org/dc/elements/1.1/subject" }, "source" : { "@id" : "http://purl.org/dc/elements/1.1/source" }, "language" : { "@id" : "http://purl.org/dc/elements/1.1/language" }, "title" : { "@id" : "http://purl.org/dc/elements/1.1/title" }, "description" : { "@id" : "http://purl.org/dc/elements/1.1/description" }, "identifier" : { "@id" : "http://purl.org/dc/elements/1.1/identifier" }, "created" : { "@id" : "http://purl.org/dc/terms/created" }, "creator" : { "@id" : "http://purl.org/dc/elements/1.1/creator" }, "contributor" : { "@id" : "http://purl.org/dc/elements/1.1/contributor" }, "rights" : { "@id" : "http://www.europeana.eu/schemas/edm/rights" }, "provider" : { "@id" : "http://www.europeana.eu/schemas/edm/provider" }, "isShownAt" : { "@id" : "http://www.europeana.eu/schemas/edm/isShownAt", "@type" : "@id" }, "dataProvider" : { "@id" : "http://www.europeana.eu/schemas/edm/dataProvider" }, "aggregatedCHO" : { "@id" : "http://www.europeana.eu/schemas/edm/aggregatedCHO", "@type" : "@id" }, "note" : { "@id" : "http://www.w3.org/2004/02/skos/core#note" }, "exactMatch" : { "@id" : "http://www.w3.org/2004/02/skos/core#exactMatch", "@type" : "@id" }, "narrower" : { "@id" : "http://www.w3.org/2004/02/skos/core#narrower", "@type" : "@id" }, "narrowMatch" : { "@id" : "http://www.w3.org/2004/02/skos/core#narrowMatch", "@type" : "@id" }, "broader" : { "@id" : "http://www.w3.org/2004/02/skos/core#broader", "@type" : "@id" }, "prefLabel" : { "@id" : "http://www.w3.org/2004/02/skos/core#prefLabel" }, "ore" : "http://www.openarchives.org/ore/terms/", "owl" : "http://www.w3.org/2002/07/owl#", "svcs" : "http://rdfs.org/sioc/services#", "skos" : "http://www.w3.org/2004/02/skos/core#", "rdfs" : "http://www.w3.org/2000/01/rdf-schema#", "rdaGr2" : "http://rdvocab.info/ElementsGr2/", "edm" : "http://www.europeana.eu/schemas/edm/", "ekt" : "https://www.semantics.gr/authorities/schemanamespaces/ekt#", "doap" : "http://usefulinc.com/ns/doap#", "rdf" : "http://www.w3.org/1999/02/22-rdf-syntax-ns#", "xalan" : "http://xml.apache.org/xalan", "dcterms" : "http://purl.org/dc/terms/", "wgs84_pos" : "http://www.w3.org/2003/01/geo/wgs84_pos#", "foaf" : "http://xmlns.com/foaf/0.1/", "crm" : "http://www.cidoc-crm.org/rdfs/cidoc_crm_v5.0.2_english_label.rdfs#", "dc" : "http://purl.org/dc/elements/1.1/" } }