Effects of nucleus pulposus on nerve root circulation and function. Morphologic and functional studies in an experimental model using porcine spinal nerve roots

Sciatica due to lumbar disc herniation has for many decades been viewed as a consequence of mechanical compression exerted on spinal nerve roots by the bulging disc tissues. Recent research has, however, indicated that extruded nucleus pulposus (NP) from the intervertebral disc might cause functional and endoneurial morphological changes in spinal nerve roots, without mechanical compression. However, the mechanisms by which an epidurally applied substance may reach and subsequently affect the endoneurial environment, and the time course for such a process, have not been established.In the present investigation, an experimental animal model was used in which the early circulatory and functional responses in the porcine sacral spinal nerve roots and cauda equina following epidural application of autologous NP were studied. Using Evans blue albumin (EBA) and horseradish peroxidase (HRP) as tracers, the model was also used to assess the existence of a transport route from the epidural to the endoneurial space of spinal nerve roots for macromolecules. This was performed by means of fluorescence-, light-, and electron microscopy. HRP was detected endoneurially in dorsal root ganglia (DRG) after 5 minutes of epidural application, while EBA was detected inside nerve root and DRG capillaries after 1 minute of epidural application. In NP-exposed nerve roots, endoneurial oedema and hyperemia developed within 2 hours and a reduction in nerve conduction velocity (NCV) developed within 7 days. It was possible to partially prevent these changes using high dose methyl prednisolone (30mg/kg) treatment.In summary, these data indicate the existence of a transport route for epidurally applied substances to the endoneurial space of spinal nerve roots and DRG. The data also indicate that epidural application of NP on the spinal nerve roots may induce early endoneurial circulatory and functional changes. The demonstrated transport route might be involved in these changes by providing neurotoxic substances an easy access to the endoneurial space. The possibility to partially prevent the demonstrated changes by a systemically administered, anti-inflammatory treatment, indicates the presence of an in situ ongoing inflammatory respons