Patofisiología del disco relacionado con el dolor lumbar y ciática….(I)

Denis Mullemana, b, Saloua Mammoub, Isabelle Griffoulb, Hervé Watiera and Philippe Goupillea, b, ,

aFrançois Rabelais de Tours University, EA 3853 Immuno-Pharmaco-genetics of Therapeutic Antibodies (IPGA), Tours, France bRheumatology Department, CHU, Trousseau Teaching Hospital, 37044 Tours cedex 9, France

Abstract

Strong evidence suggests that TNF-α may be among the chemical factors involved in disk-related sciatica. TNF-α 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-α has been identified in nucleus pulposus and Schwann cells. Local production of endogenous TNF-α may occur early in the pathogenic process. Exposure to exogenous TNF-α 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-α 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-α 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-α antagonists. Thus, whether TNF-α antagonist therapy is warranted in patients with disk-related sciatica remains an open question, and further randomized controlled studies are needed.