title: Direct application of the TNF-alpha inhibitor, etanercept, does not affect CGRP expression and phenotypic change of DRG neurons following application of nucleus pulposus onto injured sciatic nerves in rats.
abstract: METHODS
  Immunohistological and behavioral analysis of the effect of a tumor necrosis factor alpha (TNF-alpha) inhibitor in an injured-nerve model.
  
  
  OBJECTIVE
  To examine the effect of direct application of a TNF-alpha inhibitor (etanercept) on injured-nerve pain caused by nucleus pulposus.
  
  
  BACKGROUND
  TNF-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.
  
  
  METHODS
  For 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.
  
  
  RESULTS
  Significant 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).
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Norimoto
authors.forename: Seiji
authors.initials: S
authors.lastname: Ohtori
authors.forename: Masaomi
authors.initials: M
authors.lastname: Yamashita
authors.forename: Gen
authors.initials: G
authors.lastname: Inoue
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Yamauchi
authors.forename: Takana
authors.initials: T
authors.lastname: Koshi
authors.forename: Munetaka
authors.initials: M
authors.lastname: Suzuki
authors.forename: Sumihisa
authors.initials: S
authors.lastname: Orita
authors.forename: Yawara
authors.initials: Y
authors.lastname: Eguchi
authors.forename: Ai
authors.initials: A
authors.lastname: Sugiura
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Ochiai
authors.forename: Masashi
authors.initials: M
authors.lastname: Takaso
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D004195:Disease Models, Animal; D000068800:Etanercept; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism; D007074:Immunoglobulin G / Q000494:pharmacology*; D007405:Intervertebral Disc Displacement / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D009437:Neuralgia / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor; D012584:Sciatic Nerve / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D015740:Calcitonin Gene-Related Peptide; D000068800:Etanercept