1: Spine. 2001 Apr 15;26(8):863-9.  

Selective inhibition of tumor necrosis factor-alpha prevents nucleus
pulposus-induced thrombus formation, intraneural edema, and reduction of nerve
conduction velocity: possible implications for future pharmacologic treatment
strategies of sciatica.

Olmarker K, Rydevik B.

Department of Orthopaedics, Goteborg University, Gothenburg, Sweden.

STUDY DESIGN: The possibility to prevent nucleus pulposus-induced functional and
structural nerve root injury by selective tumor necrosis factor-alpha inhibition
was assessed in an experimental model in the pig spine. OBJECTIVE: The objective
of the study was to evaluate the role of tumor necrosis factor-alpha in the
mediation of nucleus pulposus-induced nerve injury by using selective
inhibition. SUMMARY OF BACKGROUND DATA: The cytokine tumor necrosis factor-alpha
has been suggested to play a key role in the nerve root injury induced by local
application of nucleus pulposus. However, previous studies have not been able to
distinguish the effects between tumor necrosis factor-alpha and other
disc-related cytokines because of the use of nonspecific cytokine inhibition.
METHODS: Autologous nucleus pulposus was harvested from a lumbar disc and
applied to the porcine sacrococcygeal cauda equina. The pigs were simultaneously
treated with two selective tumor necrosis factor-alpha inhibitors (etanercept n
= 8 and infliximab n = 5), a heparin analogue (enoxaparin n = 5) or saline for
control (n = 5). After 7 days the nerve conduction velocity over the application
zone was determined and samples of the exposed nerve roots were collected for
light microscopic evaluation. RESULTS: The two tumor necrosis factor-alpha
inhibitors prevented the reduction of nerve conduction velocity and also seemed
to limit the nerve fiber injury, the intracapillary thrombus formation, and the
intraneural edema formation. However, treatment with enoxaparin did not seem to
be different from control regarding reduction of nerve conduction velocity or
histologic changes. CONCLUSIONS: The data clearly indicate that tumor necrosis
factor-alpha is involved in the basic pathophysiologic events leading to nerve
root structural and functional changes after local application of nucleus
pulposus. The study therefore provides a basic scientific platform with
potential clinical implications regarding the use of anti-tumor necrosis
factor-alpha medication as treatment in patients with disc herniation and
sciatica.

PMID: 11317106 [PubMed - indexed for MEDLINE]