{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:01:13Z","timestamp":1790190073713,"version":"4.1.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T00:00:00Z","timestamp":1646352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Academy of Medical Sciences Springboard","award":["RE15263"],"award-info":[{"award-number":["RE15263"]}]},{"name":"National Centre for the Replacement, Refinement and Reduction of Animals in Research studentship","award":["NC\/T002115\/1"],"award-info":[{"award-number":["NC\/T002115\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Brainstem to spinal cord noradrenergic pathways include a locus coeruleus origin projection and diffuse noxious inhibitory controls. While both pathways are traditionally viewed as exerting an inhibitory effect on spinal neuronal activity, the locus coeruleus was previously shown to have a facilitatory influence on thermal nocioception according to the subpopulation of coerulean neurons activated. Coupled with knowledge of its functional modular organisation and the fact that diffuse noxious inhibitory controls are not expressed in varied animal models of chronicity, we hypothesized a regulatory role for the locus coeruleus on non-coerulean, discrete noradrenergic cell group(s).<\/jats:p>\n                  <jats:p>We implemented locus coeruleus targeting strategies by microinjecting canine adenovirus encoding for channelrhodopsin-2 under a noradrenaline-specific promoter in the spinal cord (retrogradely labelling a coeruleospinal module) or the locus coeruleus itself (labelling the entire coerulean module). Coeruleospinal module optoactivation abolished diffuse noxious inhibitory controls (two-way ANOVA, P\u2009&amp;lt;\u20090.0001), which were still expressed following locus coeruleus neuronal ablation.<\/jats:p>\n                  <jats:p>We propose that the cerulean system interacts with, but does not directly govern, diffuse noxious inhibitory controls. This mechanism may underlie the role of the locus coeruleus as a \u2018chronic pain generator\u2019. Pinpointing the functionality of discrete top-down pathways is crucial for understanding sensorimotor modulation in health and disease.<\/jats:p>","DOI":"10.1093\/brain\/awac085","type":"journal-article","created":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T15:12:27Z","timestamp":1646233947000},"page":"2293-2300","source":"Crossref","is-referenced-by-count":41,"title":["Distinct brainstem to spinal cord noradrenergic pathways inversely regulate spinal neuronal activity"],"prefix":"10.1093","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9081-6753","authenticated-orcid":false,"given":"Mateusz W","family":"Kucharczyk","sequence":"first","affiliation":[{"name":"Central Modulation of Pain, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London , London SE1 1UL , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Di Domenico","sequence":"additional","affiliation":[{"name":"Central Modulation of Pain, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London , London SE1 1UL , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsty","family":"Bannister","sequence":"additional","affiliation":[{"name":"Central Modulation of Pain, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London , London SE1 1UL , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,3,4]]},"reference":[{"key":"2022072919100469700_awac085-B1","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1146\/annurev.ne.14.030191.001251","article-title":"Neurotransmitters in nociceptive modulatory circuits","volume":"14","author":"Fields","year":"1991","journal-title":"Annu Rev Neurosci"},{"issue":"3","key":"2022072919100469700_awac085-B2","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/0304-3959(79)90049-6","article-title":"Diffuse noxious inhibitory controls (DNIC). 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