Pathophysiology of disk-related sciatica. I.--Evidence supporting a chemical component

Joint Bone Spine. 2006 Mar;73(2):151-8. doi: 10.1016/j.jbspin.2005.03.003. Epub 2005 Jun 22.


Sciatica in patients with disk disease was long ascribed to pressure put on the sciatic nerve root by a herniated disk. However, a role for chemical factors acting in conjunction with this mechanical insult is suggested by a number of clinical observations: disk surgery does not consistently provide pain relief, large disk herniations are not always symptomatic, severe pain may be present in patients without imaging evidence of nerve root compression, the severity of symptoms and neurological signs is not well correlated with the size of the disk herniation, and conservative therapy is often effective. Experimental studies have provided further evidence for a chemical component: disk herniations can undergo spontaneous resorption, the intervertebral disk is immunogenic, and mediators for inflammation have been identified within intervertebral disk tissue. The current pathophysiological theory incriminates proinflammatory substances secreted by the nucleus pulposus (NP). When preexisting or concomitant mechanical injury to a nerve root occurs, these substances can cause nerve root pain. Animal experiments have established that the NP can induce functional and structural nerve root abnormalities in the absence of mechanical compression and that this effect is mediated by substances located at the surface of NP cells. Methylprednisolone, diclofenac, indomethacin, doxycycline, and cyclosporine induce variable inhibition of this effect. Available information points to tumor necrosis factor-alpha (TNF-alpha) as the main candidate among substances potentially responsible for nerve root pain. Therefore, trials of TNF-alpha antagonists in patients with disk-related sciatica are warranted.

Publication types

  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Humans
  • Intervertebral Disc / immunology
  • Intervertebral Disc / metabolism*
  • Intervertebral Disc Displacement / complications
  • Intervertebral Disc Displacement / metabolism
  • Intervertebral Disc Displacement / physiopathology*
  • Pain / physiopathology*
  • Radiculopathy / physiopathology*
  • Sciatica / etiology
  • Sciatica / metabolism
  • Sciatica / physiopathology*
  • Spinal Nerve Roots / physiopathology*