{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:13:36Z","timestamp":1791288816410,"version":"4.3.0"},"reference-count":70,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mol Pain"],"published-print":{"date-parts":[[2014,1,1]]},"abstract":"<jats:sec><jats:title>Background:<\/jats:title><jats:p> Descending control of nociceptive processing, by pathways originating in the rostral ventromedial medulla (RVM) and terminating in the dorsal horn, contributes to behavioural hypersensitivity in a number of pain models. Two facilitatory pathways have been identified and are characterized by serotonin (5-HT) content or expression of the mu opiate receptor. Here we investigated the contribution of these pathways to inflammatory joint pain behaviour and gene expression changes in the dorsal horn. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p> Selective lesion of the descending serotonergic (5-HT) pathway by prior intrathecal administration of 5,7-dihydroxytryptamine attenuated hypersensitivity at early time points following ankle injection of CFA. In a separate study ablation of the mu opioid receptor expressing (MOR+) cells of the RVM, by microinjection of the toxin dermorphin-saporin, resulted in a more prolonged attenuation of hypersensitivity post CFA. Microarray analysis was carried out to identify changes in dorsal horn gene expression associated with descending facilitation by the MOR+ pathway at 7d post joint inflammation. This analysis led to the identification of a number of genes including the chemokines Cxcl9 and Cxcl10, their common receptor Cxcr3, and the proinflammatory gene Nos2 (inducible nitric oxide synthase, iNOS). <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p> These findings demonstrate that joint pain behaviour is dependent in part on descending facilitation via the RVM, and identify a novel pathway driving CXC chemokine and iNOS expression in the dorsal horn. <\/jats:p><\/jats:sec>","DOI":"10.1186\/1744-8069-10-39","type":"journal-article","created":{"date-parts":[[2014,6,20]],"date-time":"2014-06-20T05:02:42Z","timestamp":1403240562000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":21,"title":["Descending Controls Modulate Inflammatory Joint Pain and Regulate CXC Chemokine and iNOS Expression in the Dorsal Horn"],"prefix":"10.1177","volume":"10","author":[{"given":"Fiona B","family":"Carr","sequence":"first","affiliation":[{"name":"Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine M","family":"G\u00e9ranten","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen P","family":"Hunt","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, University College London, London WC1E 6BT, 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