Hess, Andreas and Axmann, Roland and Rech, Juergen and Finzel, Stefanie and Heindl, Cornelia and Kreitz, Silke and Sergeeva, Marina and Saake, Marc and Garcia, Meritxell and Kollias, George and Straub, Rainer H. and Sporns, Olaf and Doerfler, Arnd and Brune, Kay and Schett, Georg (2011) Blockade of TNF-alpha rapidly inhibits pain responses in the central nervous system. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 108 (9). pp. 3731-3736. ISSN 0027-8424,
Full text not available from this repository. (Request a copy)Abstract
There has been a consistent gap in understanding how TNF-alpha 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-alpha 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-alpha, 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-alpha. In contrast, clinical and laboratory markers of inflammation, such as joint swelling and acute phase reactants, were not affected by anti-TNF-alpha at these early time points. Moreover, arthritic mice over-expressing human TNF-alpha 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-alpha. These results suggest that neutralization of TNF-alpha affects nociceptive brain activity in the context of arthritis, long before it achieves anti-inflammatory effects in the joints.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR-NECROSIS-FACTOR; RHEUMATOID-ARTHRITIS; FUNCTIONAL MRI; MICE; HYPERALGESIA; OXYGENATION; MECHANISMS; ANTIBODY; BEHAVIOR; DISEASE; cytokines; antiinflammatory therapy |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 25 Jun 2020 09:44 |
| Last Modified: | 25 Jun 2020 09:44 |
| URI: | https://pred.uni-regensburg.de/id/eprint/21248 |
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