title: Elevated levels of tumor necrosis factor-α and TNFR1 in recurrent herniated lumbar discs correlate with chronicity of postoperative sciatic pain.
abstract: BACKGROUND
  Sciatica is a condition characterized by radicular pain that can be secondary to a lumbar disc herniation (LDH). More than 10% of patients report persistent pain after surgery. The underlying mechanisms of postoperative sciatica remain unclear. There is evidence demonstrating that inflammation plays a role in the pathophysiology of sciatica.
  
  
  OBJECTIVE
  The study aimed to assess if the expression of tumor necrosis factor (TNF)-α and its receptors (TNFR) was correlated with the severity of pre- and postoperative leg pain in LDH patients who underwent single or multiple decompressive discectomies.
  
  
  METHODS
  This is an experimental prospective human study of intraoperative intervertebral disc (IVD) samples, as well as a clinical scores evaluation.
  
  
  METHODS
  We analyzed the mRNA and protein levels of TNF-α, TNFR1, and TNFR2 in IVD biopsies, and correlated them with visual analogue scale (VAS) scores 1 day before surgery to 6 weeks and 6 months postoperatively.
  
  
  RESULTS
  We evaluated the correlation between the inflammation in IVD with pre- and postoperative pain scores after discectomy in LDH patients operated for the first time (fLDH, N=12) and for recurrent cases (rLDH, N=8). This analysis showed that TNF-α and TNFR1 mRNA levels were significantly greater in rLDH patients; there was a twofold increase for TNF-α and a 50% increase for TNFR1. Similarly, protein levels in IVD samples positively correlated with postoperative VAS scores, whereas TNFR2 protein levels negatively correlated with postoperative VAS scores.
  
  
  CONCLUSIONS
  These findings indicate that rLDH patients present higher postoperative VAS scores compared with fLDH patients, and also that these scores are correlated with increased inflammation and may contribute to pain chronicity.
authors.affiliation: Department of Neurosurgery, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX, Maastricht, The Netherlands; Department of Neuroscience, Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, The Netherlands; Department of Neurosurgery, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany. Electronic address: pablo.andrade-montemayor@uk-koeln.de.
authors.forename: Pablo
authors.initials: P
authors.lastname: Andrade
authors.affiliation: Department of Neurosurgery, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX, Maastricht, The Netherlands; Department of Neuroscience, Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, The Netherlands.
authors.forename: Govert
authors.initials: G
authors.lastname: Hoogland
authors.affiliation: Department of Neurosurgery, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX, Maastricht, The Netherlands.
authors.forename: Onno P
authors.initials: OP
authors.lastname: Teernstra
authors.affiliation: Department of Neurosurgery, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX, Maastricht, The Netherlands.
authors.forename: Jasper
authors.initials: J
authors.lastname: van Aalst
authors.affiliation: Department of Neurosurgery, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX, Maastricht, The Netherlands.
authors.forename: Emiel
authors.initials: E
authors.lastname: van Maren
authors.affiliation: Department of Neurosurgery, Kliniek Klein Rosendael, Rosendaalselaan 30, 6891 DG, Rozendaal, The Netherlands.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Daemen
authors.affiliation: Department of Neurosurgery, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX, Maastricht, The Netherlands; Department of Stereotactic and Functional Neurosurgery, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
authors.forename: Veerle
authors.initials: V
authors.lastname: Visser-Vandewalle
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D006801:Humans; D007403:Intervertebral Disc / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D007405:Intervertebral Disc Displacement / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D019635:Neurosurgical Procedures / Q000009:adverse effects; D010149:Postoperative Pain / Q000209:etiology / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism*; D012585:Sciatica / Q000209:etiology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha
keywords: Chronic pain; Discectomy; Intervertebral disc; Leg pain; Lumbar disc herniation; Neuroinflammation; Pain; Sciatica; TNF-α; TNF-α receptors