Blockade of TNF-α rapidly inhibits pain responses in the central nervous system

Heß A, Axmann R, Rech J, Finzel S, Heindl-Erdmann C, Kreitz S, Sergeeva M, Saake M, Garcia M, Kollias G, Straub RH, Sporns O, Dörfler A, Brune K, Schett G (2011)

Publication Type: Journal article

Publication year: 2011

Journal

Proceedings of the National Academy of Sciences of the United States of America National Academy of Sciences

Book Volume: 108

Pages Range: 3731-3736

Journal Issue: 9

DOI: 10.1073/pnas.1011774108

Abstract

There has been a consistent gap in understanding how TNF-α 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-α 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-α, 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-α. In contrast, clinical and laboratory markers of inflammation, such as joint swelling and acute phase reactants, were not affected by anti-TNF-α at these early time points. Moreover, arthritic mice overexpressing human TNF-α showed an altered pain behavior and amore 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-α. These results suggest that neutralization of TNF-α affects nociceptive brain activity in the context of arthritis, long before it achieves antiinflammatory effects in the joints.

Authors with CRIS profile

Andreas Heß Medizinische Fakultät Hans Jürgen Rech Department of Medicine 3 – Rheumatology and Immunology Stephanie Finzel Lehrstuhl für Innere Medizin III Cornelia Heindl-Erdmann Lehrstuhl für Pharmakologie und Toxikologie Silke Kreitz Lehrstuhl für Pharmakologie und Toxikologie Marina Sergeeva Lehrstuhl für Pharmakologie und Toxikologie Marc Saake Medizinische Fakultät Arnd Dörfler Department of Neuroradiology Kay Brune Medizinische Fakultät Georg Schett Lehrstuhl für Innere Medizin III

Involved external institutions

Indiana University US United States (USA) (US) Biomedical Sciences Research Center "Alexander Fleming" GR Greece (GR) Universität Regensburg DE Germany (DE)

How to cite

APA:

Heß, A., Axmann, R., Rech, J., Finzel, S., Heindl-Erdmann, C., Kreitz, S.,... Schett, G. (2011). Blockade of TNF-α rapidly inhibits pain responses in the central nervous system. Proceedings of the National Academy of Sciences of the United States of America, 108(9), 3731-3736. https://doi.org/10.1073/pnas.1011774108

MLA:

Heß, Andreas, et al. "Blockade of TNF-α rapidly inhibits pain responses in the central nervous system." Proceedings of the National Academy of Sciences of the United States of America 108.9 (2011): 3731-3736.

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