Studies have been performed to elucidate the pathophysiologic mechanisms leading to sciatica. The studies comprise assessment of structural and functional changes as well as pain and have shown that the intervertebral disk (nucleus pulposus) may induce changes in a nerve root after local application in the absence of a mechanical component. Such changes may for the first time present a biologic or biochemical basis for the development of sciatica. Disk-related cytokines, in particular tumor necrosis factor (TNF), have been found to mediate such changes, and clinical trials have now been initiated to assess the possibility of treating sciatica with selective inhibition of TNF.