• Masaki Norimoto, Seiji Ohtori, Masaomi Yamashita, Gen Inoue, Kazuyo Yamauchi, Takana Koshi, Munetaka Suzuki, Sumihisa Orita, Yawara Eguchi, Ai Sugiura, Nobuyasu Ochiai, Masashi Takaso, and Kazuhisa Takahashi.
• Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Japan.
• Spine. 2008 Oct 15;33(22):2403-8.

Study DesignImmunohistological and behavioral analysis of the effect of a tumor necrosis factor alpha (TNF-alpha) inhibitor in an injured-nerve model.ObjectiveTo examine the effect of direct application of a TNF-alpha inhibitor (etanercept) on injured-nerve pain caused by nucleus pulposus.Summary And Background DataTNF-alpha is thought to play a crucial role in radicular pain. Calcitonin gene-related peptide (CGRP) is an inflammatory neuropeptide found in small sensory neurons. We have reported that CGRP appears in medium and large dorsal root ganglion (DRG) neurons that transmit proprioception in physiologic conditions. The purpose of the current study was to examine the change in behavior and phenotypic change of CGRP-immunoreactive DRG neurons by the TNF-alpha inhibitor, etanercept, in a disc herniation model.MethodsFor the injured-nerve model, nucleus pulposus was applied to the sciatic nerve and the sciatic nerve pinched. Saline (10 microL; n = 10), as a control, or etanercept (150 microg: n = 10) were applied to sciatic nerves simultaneously. Mechanical allodynia was examined. Immunohistochemistry was used to examine CGRP expression in L5 DRGs.ResultsSignificant mechanical allodynia for 10 days was seen in the injured-nerve group compared with sham-operated animals. Etanercept ameliorated the mechanical allodynia slightly on day 2; however, there was no effect on other days. CGRP immunoreactivity was upregulated in the L5 DRG neurons of injured-nerve groups compared with the sham-operated group (P < 0.01). However, etanercept did not affect CGRP expression after nerve injury (P > 0.05). Proportions of CGRP- immunoreactive medium and large neurons were not significantly different in the nerve injury + saline group compared with the injury + etanercept group (P > 0.05).ConclusionOur results indicate that direct application of a TNF-alpha inhibitor had a small effect on acute pain behavior and may not be effective for suppression of inflammatory peptides in the current disc-herniation model.

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