title: Infliximab attenuates immunoreactivity of brain-derived neurotrophic factor in a rat model of herniated nucleus pulposus.
abstract: METHODS
  The effect of infliximab, a chimeric monoclonal antibody to TNF-alpha, on induction of brain-derived neurotrophic factor (BDNF) was examined using an experimental herniated nucleus pulposus (NP) model.
  
  
  OBJECTIVE
  To investigate whether treatment of infliximab could attenuate an induction of BDNF, which functions as a modulator of pain, following NP application to the nerve root.
  
  
  BACKGROUND
  Evidence from basic scientific studies proposes that TNF-alpha is involved in the development of NP-induced nerve injuries. However, the therapeutic mechanisms of infliximab against pain have not been elucidated experimentally.
  
  
  METHODS
  Twenty rats were used in this study. In the test groups, the animals underwent application of NP to the L4 nerve roots and received a single systemic (intraperitoneal) injection of infliximab at the time of surgery (Infli-0 group, n = 5) or at 1 day after operation (Infli-1 group, n = 5). As a control treatment, sterile water was administered intraperitoneally to 5 rats with NP application (NP group) and to 5 sham-operated rats (sham group). On day 3 after surgery, the L4 dorsal root ganglion (DRG) and L4 spinal segment were harvested and assessed regarding BDNF immunoreactivity. RESULTS.: Application of NP induced a marked increase of BDNF immunoreactivity in number in the DRG neurons and within the superficial layer in the dorsal horn compared with the sham group (P < 0.01). Infliximab treatment in the Infli-0 and Infli-1 groups reduced the BDNF induction in both DRG and spinal cord (P < 0.05).
  
  
  CONCLUSIONS
  These findings indicate that infliximab attenuates the elevated BDNF levels induced by NP. The present study therefore further indicates the importance of TNF-alpha in sciatica due to disc herniation and the possible therapeutic use of a TNF-alpha inhibitor for this condition.
authors.affiliation: Department of Orthopaedics, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden.
authors.forename: Akira
authors.initials: A
authors.lastname: Onda
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Murata
authors.forename: Björn
authors.initials: B
authors.lastname: Rydevik
authors.forename: Karin
authors.initials: K
authors.lastname: Larsson
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kikuchi
authors.forename: Kjell
authors.initials: K
authors.lastname: Olmarker
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D005260:Female; D005727:Ganglia, Spinal / Q000737:chemistry / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects*; D000069285:Infliximab; D007405:Intervertebral Disc Displacement / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D009474:Neurons / Q000737:chemistry; D020671:Posterior Horn Cells / Q000737:chemistry / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012585:Sciatica / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D013116:Spinal Cord / Q000737:chemistry / Q000473:pathology; D013126:Spinal Nerve Roots
chemical_list: D000911:Antibodies, Monoclonal; D019208:Brain-Derived Neurotrophic Factor; D000069285:Infliximab