{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["108(9)"],"submitter":["Hess A"],"pubmed_abstract":["There has been a consistent gap in understanding how TNF-? neutralization affects the disease state of arthritis patients so rapidly, considering that joint inflammation in rheumatoid arthritis is a chronic condition with structural changes. We thus hypothesized that neutralization of TNF-? acts through the CNS before directly affecting joint inflammation. Through use of functional MRI (fMRI), we demonstrate that within 24 h after neutralization of TNF-?, 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-?. In contrast, clinical and laboratory markers of inflammation, such as joint swelling and acute phase reactants, were not affected by anti-TNF-? at these early time points. Moreover, arthritic mice overexpressing human TNF-? 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-?. These results suggest that neutralization of TNF-? affects nociceptive brain activity in the context of arthritis, long before it achieves anti-inflammatory effects in the joints."],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pagination":["3731-6"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3048151"],"repository":["biostudies-literature"],"pubmed_title":["Blockade of TNF-? rapidly inhibits pain responses in the central nervous system."],"pmcid":["PMC3048151"],"pubmed_authors":["Brune K","Sergeeva M","Rech J","Sporns O","Garcia M","Saake M","Kollias G","Kreitz S","Finzel S","Doerfler A","Heindl C","Straub RH","Hess A","Schett G","Axmann R"],"additional_accession":[]},"is_claimable":false,"name":"Blockade of TNF-? rapidly inhibits pain responses in the central nervous system.","description":"There has been a consistent gap in understanding how TNF-? neutralization affects the disease state of arthritis patients so rapidly, considering that joint inflammation in rheumatoid arthritis is a chronic condition with structural changes. We thus hypothesized that neutralization of TNF-? acts through the CNS before directly affecting joint inflammation. Through use of functional MRI (fMRI), we demonstrate that within 24 h after neutralization of TNF-?, 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-?. In contrast, clinical and laboratory markers of inflammation, such as joint swelling and acute phase reactants, were not affected by anti-TNF-? at these early time points. Moreover, arthritic mice overexpressing human TNF-? 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-?. These results suggest that neutralization of TNF-? affects nociceptive brain activity in the context of arthritis, long before it achieves anti-inflammatory effects in the joints.","dates":{"release":"2011-01-01T00:00:00Z","publication":"2011 Mar","modification":"2021-02-20T14:40:18Z","creation":"2019-03-27T00:39:19Z"},"accession":"S-EPMC3048151","cross_references":{"pubmed":["21245297"],"doi":["10.1073/pnas.1011774108"]}}