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Abstract #3656

Translational BOLD FMRI in Mice and Man: Precinical and Clinical Treatment Approaches

Andreas Hess1, Juergen Rech2, Arnd Doerfler3, Georg Kollias4, Olaf Sporns5, Georg Schett2

1Institute of Experimental and Clinical Pharmacology and Toxicology, FAU Erlangen-Nuremberg, Erlangen, Germany; 2Department of Internal Medicine 3, Erlangen, Germany; 3of Neuroradiology, FAU Erlangen-Nuremberg, Erlangen, Germany; 4Institute of Immunology; Alexander Fleming Biomedical Sciences Research Center, Vari, Greece; 5Department of Psychological and Brain Sciences, Programs in Neuroscience and Cognitive Science, IN, United States

Pain is the key symptom in patients with arthritis. We hypothesized that hypernociception due to chronic TNF overexpression leads to an altered pain processing. Using fMRI we demonstrated that mice overexpressing human tumor necrosis factor (hTNF), as well as rheumatoid arthritis patients exhibit more intensive brain activity upon nociceptive stimuli. Graph-theoretical connectivity analysis showed rewiring under chronic pain conditions i.e. tight clustering of thalamus and periaqueductal grey. Neutralization of TNF by antibodies rapidly reversed this hypernociception in mice and men. This similarity of pain related effects in mouse and man facilitates a translational approach for searching for novel analgesics.

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Keywords

account activated activity adaptation allow analgesics anatomic anatomical antibodies antibody approaches array arthritis atlas axial belonging biomedical bold brain certain channel chronic classical clinical clinically clustering cognitive coil compression computed conditions connectivity consumer contact corrected correlation cradle cross crossing days decrease determined discarded dissociation edges equal exhibit experimental extensive force functional global graph head heat human humans immediately immunology inflammatory infusion inside institute intensive interpolation interval invasive joints labeled lead length long matrices matrix medicine mice minutes modern monitoring mouse necrosis networks neutralization next normalize novel overall pain patients pharmacology physiological placed predictors procedure processing programs psychological quadrature rapidly rare received recorded reduction reflected related residuals response reversed rheumatoid scanner scanning science sciences searching separate session sets shot since slice slices smoothing software spin stimulation stimuli stimulus structures success system tapping temporal thalamus therapeutic thresholded tight toxicology translational treatment trio tumor typically upon version view visualized volumes voyager weeks whole widespread