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Through use of functional MRI (fMRI), we demonstrate that within 24 h after neutralization of TNF-\u03b1, nociceptive CNS activity in the thalamus and somatosensoric cortex, but also the activation of the limbic system, is blocked. Brain areas showing blood-oxygen level-dependent signals, a validated method to assess neuronal activity elicited by pain, were significantly reduced as early as 24 h after an infusion of a monoclonal antibody to TNF-\u03b1. In contrast, clinical and laboratory markers of inflammation, such as joint swelling and acute phase reactants, were not affected by anti-TNF-\u03b1 at these early time points. Moreover, arthritic mice overexpressing human TNF-\u03b1 showed an altered pain behavior and a more intensive, widespread, and prolonged brain activity upon nociceptive stimuli compared with wild-type mice. Similar to humans, these changes, as well as the rewiring of CNS activity resulting in tight clustering in the thalamus, were rapidly reversed after neutralization of TNF-\u03b1. These results suggest that neutralization of TNF-\u03b1 affects nociceptive brain activity in the context of arthritis, long before it achieves anti-inflammatory effects in the joints.<\/jats:p>","DOI":"10.1073\/pnas.1011774108","type":"journal-article","created":{"date-parts":[[2011,1,19]],"date-time":"2011-01-19T00:04:46Z","timestamp":1295395486000},"page":"3731-3736","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":348,"title":["Blockade of TNF-\u03b1 rapidly inhibits pain responses in the central nervous system"],"prefix":"10.1073","volume":"108","author":[{"given":"Andreas","family":"Hess","sequence":"first","affiliation":[{"name":"Institute of Experimental and Clinical Pharmacology and Toxicology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Axmann","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 3, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juergen","family":"Rech","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 3, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Finzel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 3, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Heindl","sequence":"additional","affiliation":[{"name":"Institute of Experimental and Clinical Pharmacology and Toxicology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"Kreitz","sequence":"additional","affiliation":[{"name":"Institute of Experimental and Clinical Pharmacology and Toxicology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Sergeeva","sequence":"additional","affiliation":[{"name":"Institute of Experimental and Clinical Pharmacology and Toxicology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Saake","sequence":"additional","affiliation":[{"name":"Division of Neuroradiology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meritxell","family":"Garcia","sequence":"additional","affiliation":[{"name":"Division of Neuroradiology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Kollias","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Alexander Fleming Biomedical Sciences Research Center, 16672 Vari, Greece;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer H.","family":"Straub","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University of Regensburg, 93053 Regensburg, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Sporns","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences, Programs in Neuroscience and Cognitive Science, Indiana University, Bloomington, IN 47405"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnd","family":"Doerfler","sequence":"additional","affiliation":[{"name":"Division of Neuroradiology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kay","family":"Brune","sequence":"additional","affiliation":[{"name":"Institute of Experimental and Clinical Pharmacology and Toxicology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Schett","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 3, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,1,18]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1109"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01661"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2094"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(89)90430-3"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201040319"},{"key":"e_1_3_3_6_2","first-page":"CD007848","article-title":"Biologics for rheumatoid arthritis: An overview of Cochrane reviews","volume":"4","author":"Singh JA","year":"2009","unstructured":"JA Singh, et al., Biologics for rheumatoid arthritis: An overview of Cochrane reviews. 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