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

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.

SUBMITTER: Hess A 

PROVIDER: S-EPMC3048151 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature