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Joint Bone Spine
Volume 73, n° 3
pages 270-277 (mai 2006)
Doi : 10.1016/j.jbspin.2005.03.004
Received : 31 January 2005 ;  accepted : 9 Mars 2005
Pathophysiology of disk-related low back pain and sciatica. II. Evidence supporting treatment with TNF- antagonists
 

Denis Mulleman a, b, Saloua Mammou b, Isabelle Griffoul b, Hervé Watier a, Philippe Goupille a, b,
a François Rabelais de Tours University, EA 3853 Immuno-Pharmaco-genetics of Therapeutic Antibodies (IPGA), Tours, France 
b Rheumatology Department, CHU, Trousseau Teaching Hospital, 37044 Tours cedex 9, France 

*Corresponding author. Tel.: +33 2 47 47 59 17; fax: +33 2 47 47 46 39.
Abstract

Strong evidence suggests that TNF- may be among the chemical factors involved in disk-related sciatica. TNF- is involved in the genesis of nerve pain in animal models and may promote pain-signal production from nerve roots previously subjected to mechanical deformation. In animal experiments, TNF- has been identified in nucleus pulposus and Schwann cells. Local production of endogenous TNF- may occur early in the pathogenic process. Exposure to exogenous TNF- induces electrophysiological, histological, and behavioral changes similar to those seen after exposure to nucleus pulposus, and these changes are more severe when mechanical compression is applied concomitantly. TNF- antagonists diminish or abolish abnormalities in animal models. Other cytokines may be involved also, as suggested by the potent inhibitory effects of compounds such as doxycycline. Two open-label studies in humans suggest dramatic efficacy of TNF- antagonists in alleviating disk-related sciatica. In contrast, the results of the only controlled study available to date do not support a therapeutic effect of TNF- antagonists. Thus, whether TNF- antagonist therapy is warranted in patients with disk-related sciatica remains an open question, and further randomized controlled studies are needed.

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Keywords : Disk-related sciatica, Tumor necrosis factor alpha, TNF- antagonists




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