Pathophysiology of disk-related low back pain and sciatica. II. Evidence supporting treatment with TNF-alpha antagonists.
Strong evidence suggests that TNF-alpha may be among the chemical factors involved in disk-related sciatica. TNF-alpha 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-alpha has been identified in nucleus pulposus and Schwann cells. Local production of endogenous TNF-alpha may occur early in the pathogenic process. Exposure to exogenous TNF-alpha 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-alpha 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-alpha 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-alpha antagonists. Thus, whether TNF-alpha antagonist therapy is warranted in patients with disk-related sciatica remains an open question, and further randomized controlled studies are needed.
Mulleman
Denis
D
François Rabelais de Tours University, EA 3853 Immuno-Pharmaco-genetics of Therapeutic Antibodies (IPGA), France.
Mammou
Saloua
S
Griffoul
Isabelle
I
Watier
Hervé
H
Goupille
Philippe
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D004318:Doxycycline / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D000069285:Infliximab; D017116:Low Back Pain / Q000188:drug therapy* / Q000503:physiopathology*; D009437:Neuralgia / Q000139:chemically induced / Q000503:physiopathology; D010431:Pentoxifylline / Q000494:pharmacology / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D051381:Rats; D012585:Sciatica / Q000188:drug therapy* / Q000503:physiopathology*; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000503:physiopathology; D013792:Thalidomide / Q000494:pharmacology / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000502:physiology
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide; D000069285:Infliximab; D004318:Doxycycline; D010431:Pentoxifylline