Since the discovery of the relationship between the occurrence of sciatica and the epidural presence of herniated disc material in 1934, the predominating theory regarding the pathophysiology of sciatica has been based on the assumption that the disc material mechanically affects the adjacent nervous structures which subsequently leads to sciatica. The treatment of choice thus became surgical removal of the herniated disc material. However, a number of observations have indicated that this “mechanical theory” may not fully explain the radiating pain of sciatica. For instance, mechanical deformation of peripheral nerves is seldom painful, and invasive intra spinal tumours most often induce neurological dysfunction and not pain. Under the assumption that the nucleus pulposus, which is the part that is herniating in the case of disc herniation, would comprise some component that independently from the mechanical deformation would induce nerve injury, an experiment was performed in 1993 in a newly developed model in the pig. This study showed, for the first time, that autologous nucleus pulposus per se induced structural injury and a marked reduction in nerve conduction velocity, and this opened a new research field. Since then, a large number of experimental studies have been performed by independent research groups mainly in Sweden, USA and Japan, on the nucleus pulposus effects. It has thereby been seen that nucleus pulposus may induce structural and functional changes in nerve roots in the absence of mechanical deformation. Nucleus pulposus is also “inflammatogenic” and also initiates pain behaviour changes by sensitising the nerve tissue. Based on these data the proinflammatory cytokine TNF (tumour necrosis factor) has been defined as one essential substance for inducing both the nerve root sensitisation and the nerve injury. Preliminary clinical trials have been started in Gothenburg for evaluating if selective inhibition of TNF may prove useful in establishing an alternative pharmacological treatment modality for sciatica.
