Effects of neutralizing antibodies to tumor necrosis factor-alpha on nucleus pulposus-induced abnormal nociresponses in rat dorsal horn neurons.
METHODS
The effect of an anti-tumor necrosis factor alpha (anti-TNFalpha) antibody on abnormal discharges caused by application of nucleus pulposus to the nerve root was investigated in an electrophysiologic study.


OBJECTIVE
To assess whether inhibition of TNFalpha can reduce nucleus pulposus-induced abnormal discharges.


BACKGROUND
It has been shown that TNFalpha, a proinflammatory cytokine, is a key pathogenic factor in the development of nucleus pulposus-induced abnormal discharges as a pain sensation. However, the electrophysiologic mechanisms involved in sciatica after disc herniation still have not been elucidated.


METHODS
Extracellular activities of wide-dynamic-range neurons were assessed in 21 rats. Autologous nucleus pulposus harvested from the tail was applied to the L5 nerve root. The animals were simultaneously treated with antibodies to TNFalpha (anti-TNF + nucleus pulposus group) and with phosphate-buffered saline (nucleus pulposus group). As a control (control group), a similar volume of muscle was applied to the nerve root with phosphate-buffered saline. Responses of wide-dynamic-range neurons to noxious and innocuous stimuli were examined for 2 hours.


RESULTS
Discharges evoked during noxious stimulation and discharges after withdrawal of stimulation in the nucleus pulposus group were significantly higher than those in the control group (P < 0.05). In the anti-TNF + nucleus pulposus group, discharges after withdrawal of stimulation were remarkably inhibited, as compared with those of the nucleus pulposus group (P < 0.05). However, evoked discharges during stimulation apparently were not inhibited. Responses to innocuous stimulation did not change throughout the measurements.


CONCLUSIONS
These data indicate that application of TNFalpha antibodies to the nerve root partially prevents the nucleus pulposus-induced abnormal nociresponses. Therefore, anti-TNFalpha treatment may have a therapeutic effect on sciatica after lumbar disc herniation.
Onda
Akira
A
Orthopaedic Surgery, Fukushima Medical University, School of Medicine, Fukushima, Japan. aonda@fmu.ac.jp
Yabuki
Shoji
S
Kikuchi
Shinichi
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects; D006930:Hyperalgesia / Q000503:physiopathology / Q000517:prevention & control; D007403:Intervertebral Disc / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology; D007405:Intervertebral Disc Displacement / Q000503:physiopathology*; D010812:Physical Stimulation; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha