A Critical Role for Dopamine D5 Receptors in Pain Chronicity in Male Mice

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dc.contributor.ORCID0000-0003-2186-6770 (Megat, S)en_US
dc.contributor.ORCID0000-0002-9646-1850 (Shiers, S)en_US
dc.contributor.ORCID0000-0001-8579-5540 (Moy, JK)en_US
dc.contributor.ORCID0000-0003-3178-8606 (Barragán-Iglesias, P)en_US
dc.contributor.ORCID0000-0002-6971-6221 (Price, TJ)en_US
dc.contributor.authorMegat, Salimen_US
dc.contributor.authorShiers, Stephanieen_US
dc.contributor.authorMoy, Jamie K.en_US
dc.contributor.authorBarragán-Iglesias, Paulinoen_US
dc.contributor.authorPradhan, Grishmaen_US
dc.contributor.authorMegat, Salimen_US
dc.contributor.authorDussor, Gregoryen_US
dc.contributor.authorPrice, Theodore J.en_US
dc.contributor.utdAuthorMegat, Salimen_US
dc.contributor.utdAuthorShiers, Stephanieen_US
dc.contributor.utdAuthorMoy, Jamie K.en_US
dc.contributor.utdAuthorBarragan-Iglesias, Paulinoen_US
dc.contributor.utdAuthorPradhan, Grishmaen_US
dc.contributor.utdAuthorSeal, Rebecca P.en_US
dc.contributor.utdAuthorDussor, Gregoryen_US
dc.contributor.utdAuthorPrice, Theodore J.en_US
dc.date.accessioned2018-10-22T19:35:32Z
dc.date.available2018-10-22T19:35:32Z
dc.date.created2018-01
dc.description.abstractDopaminergic modulation of spinal cord plasticity has long been recognized, but circuits affected by this system and the precise receptor subtypes involved in this modulation have not been defined. Dopaminergic modulation from the A11 nucleus of the hypothalamus contributes to plasticity in a model of chronic pain called hyperalgesic priming. Here we tested the hypothesis that the key receptor subtype mediating this effect is the D5 receptor (D5R). We find that a spinally directed lesion of dopaminergic neurons reverses hyperalgesic priming in both sexes and that a D1/D5 antagonist transiently inhibits neuropathic pain. We used mice lacking D5Rs (DRD5KO mice) to show that carrageenan, interleukin 6, as well as BDNF-induced hyperalgesia and priming are reduced specifically in male mice. These male DRD5KO mice also show reduced formalin pain responses and decreased heat pain. To characterize the subtypes of dorsal horn neurons engaged by dopamine signaling in the hyperalgesic priming model, we used c-fos labeling. We find that a mixed D1/D5 agonist given spinally to primed mice activates a subset of neurons in lamina III and IV of the dorsal horn that coexpress PAX2, a transcription factor for GABAergic interneurons. In line with this, we show that gabazine, a GABA-A receptor antagonist, is antihyperalgesic in primed mice exposed to spinal administration of a D1/D5 agonist. Therefore, the D5R, in males, and the D1R, in females, exert a powerful influence over spinal cord circuitry in pathological pain likely via modulation of deep dorsal horn GABAergic neurons.en_US
dc.description.departmentSchool of Behavioral and Brain Sciencesen_US
dc.description.sponsorshipNational Institutes of Health Grant R01NS065926, R01GM102575, R01NS073664.en_US
dc.identifier.bibliographicCitationMegat, Salim, Stephanie Shiers, Jamie K. Moy, Paulino Barragan-Iglesias, et al. 2018. "A critical role for dopamine D5 receptors in pain chronicity in male mice." Journal of Neuroscience 38(2), doi:10.1523/JNEUROSCI.2110-17.2017en_US
dc.identifier.issn0270-6474en_US
dc.identifier.issue2en_US
dc.identifier.urihttp://hdl.handle.net/10735.1/6220
dc.identifier.volume38en_US
dc.language.isoenen_US
dc.publisherSoc Neuroscienceen_US
dc.relation.urihttp://dx.doi.org/10.1523/JNEUROSCI.2110-17.2017en_US
dc.rightsCC BY 4.0 (Attribution)en_US
dc.rights©2018 The Authorsen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.source.journalJournal of Neuroscienceen_US
dc.subjectSpinal Cord Dorsal Hornen_US
dc.subjectNeuralgiaen_US
dc.subjectMice, Knockouten_US
dc.subjectRNA, Messengeren_US
dc.subjectNeuroligin 2en_US
dc.subjectNeuronsen_US
dc.subjectReceptors, Dopamine D5en_US
dc.subjectDopamineen_US
dc.subjectHyperalgesiaen_US
dc.subjectSex Characteristicsen_US
dc.titleA Critical Role for Dopamine D5 Receptors in Pain Chronicity in Male Miceen_US
dc.typeTexten_US
dc.type.genrearticleen_US

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