Changes in spontaneous behavior in rats exposed to experimental disc herniation are blocked by selective TNF-alpha inhibition.
METHODS
Study of pain behavior in animals by observation of changes in spontaneous behavior.


OBJECTIVE
To assess if selective inhibition of tumor necrosis factor alpha may reduce changes in spontaneous behavior induced by experimental disc herniation in the rat as previously reported.


BACKGROUND
It is known that the proinflammatory cytokine tumor necrosis factor alpha may play a key role for the nucleus pulposus-induced nerve dysfunction seen in experimental set ups. However, it is not known if tumor necrosis factor alpha is also involved in pain production induced by the same procedure.


METHODS
Thirty-two rats were used for the study. Twenty-two rats had an L4-L5 disc incision combined with a displacement of the L4 dorsal root ganglion. Twelve of these rats received an intraperitoneal injection of 0.125 mL of 10 mg/mL Remicade, and the remaining 10 were left untreated. Ten rats only had the L4-L5 disc exposed and formed the control group. The day before surgery and days 1, 3, 7, 14, and 21 after surgery, the rats were videotaped from below during a 20-minute period. The duration of four specific behaviors were determined and compared between the three experimental groups at each time point.


RESULTS
Similar to a previous study, the nontreated showed increased signs of focal pain behavior (rotation of the head towards the operated leg and lifting of the operated leg) during the first 7 postoperative days. Treatment with the tumor necrosis factor alpha-inhibitor infliximab significantly reduced this behavior. At day 14, there were no differences between the groups, and at day 21, the nontreated group displayed reduced locomotion and increased immobility, similar to previous observations. Tumor necrosis factor alpha inhibition also seemed to reduce these behaviors.


CONCLUSIONS
The data of the study clearly indicate a role for tumor necrosis factor alpha in the studied behavior changes after experimental disc herniation in the rat. Clinical trials must be performed in order to assess if there may be a clinical use for tumor necrosis factor alpha inhibition in the treatment of sciatica due to disc herniation.
Olmarker
Kjell
K
Department of Orthopaedics, Göteborg University, Sahlgrenska University Hospital, Gothenburg, Sweden. kjell.olmarker@orthop.gu.se
Nutu
Magdalena
M
Størkson
Rolf
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D000069285:Infliximab; D007405:Intervertebral Disc Displacement / Q000188:drug therapy* / Q000503:physiopathology*; D008124:Locomotion / Q000187:drug effects; D008161:Lumbosacral Region; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab