• Arthritis and rheumatism · May 2010

    Spinal tumor necrosis factor alpha neutralization reduces peripheral inflammation and hyperalgesia and suppresses autonomic responses in experimental arthritis: a role for spinal tumor necrosis factor alpha during induction and maintenance of peripheral inflammation.

    • Michael Karl Boettger, Konstanze Weber, David Grossmann, Mieczyslaw Gajda, Reinhard Bauer, Karl-Jürgen Bär, Steffen Schulz, Andreas Voss, Christian Geis, Rolf Bräuer, and Hans-Georg Schaible.
    • Institute of Physiology I, University Hospital Jena, Jena, Germany. Michael.Boettger@mti.uni-jena.de
    • Arthritis Rheum. 2010 May 1;62(5):1308-18.

    ObjectiveIn addition to the sensitization of pain fibers in inflamed tissues, the increased excitability of the spinal cord is an important mechanism of inflammatory pain. Furthermore, spinal neuronal excitability has been suggested to play a role in modulating peripheral inflammation. This study was undertaken to test the hypothesis that spinal actions of the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) add significantly to both hyperalgesia and maintenance of peripheral inflammation.MethodsRats with antigen-induced arthritis (AIA) were treated intrathecally with the TNFalpha-neutralizing compound etanercept continuously during the complete time course of AIA, which was 3 days for the acute phase and 21 days for the chronic phase. During this time, inflammation and pain-related behavior were monitored. Since a role for autonomic control of inflammation was proposed, measures from heart rate time series were obtained in the acute phase. Findings were compared with those in vehicle-treated animals and in animals receiving etanercept intraperitoneally.ResultsSpinally administered etanercept acutely reduced pain-related behavior, attenuated both the development and the maintenance of inflammation, and was superior to systemic administration. Parameters indicating autonomic modulation showed a shift toward a sympathetically dominated state in vehicle-treated animals, which was prevented by intrathecal etanercept.ConclusionOur findings indicate that spinal TNFalpha plays an important role in both pain signaling and modulation of peripheral inflammation. Thus, neutralizing this cytokine at the spinal site not only represents a putative therapeutic option for different pain syndromes, but may be directly used to attenuate peripheral inflammation.

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