title: Cerebrospinal fluid biomarkers in experimental spinal nerve root injury.
abstract: METHODS
  Cerebrospinal fluid biomarkers were evaluated in a setup using established pig models to mimic clinical disc herniation.
  
  
  OBJECTIVE
  To investigate biomarkers for nerve tissue injury, inflammation, and pain in cerebrospinal fluid after mechanical compression and/or nucleus pulposus application to spinal nerve roots.
  
  
  BACKGROUND
  The association between mechanical compression, biochemical effects of nucleus pulposus, and nerve root injury in degenerative disc disorders is incompletely investigated.
  
  
  METHODS
  The unilateral S1 nerve root was exposed in 20 pigs. The animals were divided into four groups (n = 5 each): 1) slow-onset mechanical compression with an ameroid constrictor; 2) autologous nucleus pulposus application; 3) mechanical compression plus nucleus pulposus; and 4) sham operation. After 1 week, 6 mL of cerebrospinal fluid was collected, and four structural nerve proteins, neurofilaments, S-100, glial fibrillary acidic protein, neuron-specific enolase, the proinflammatory cytokine interleukin-8, the neurotransmitter nociceptin, and substance P endopeptidase activity were analyzed using immunoassays.
  
  
  RESULTS
  The concentration of neurofilament was increased in the mechanical compression group (17.0 microg/L +/- 5.0) and in the mechanical compression plus nucleus pulposus group (19.8 +/- 12.1 microg/L) compared with the sham group (0.9 +/- 0.9 microg/L) and the nucleus pulposus group (0.4 +/- 0.1 microg/L) (P < 0.01 for both). The concentration of nociceptin was increased significantly in the mechanical compression group (24.0 +/- 8.6 fm/mL) and in the mechanical compression plus nucleus pulposus group (31.2 +/- 6.6 fm/mL) compared with the sham group (7.0 +/- 1.3 fm/mL) (P < 0.05 and P < 0.01, respectively). A correlation was found between concentrations of neurofilament and nociceptin (r = 0.50, P < 0.05). There were no intergroup differences regarding glial fibrillary acidic protein, neuron-specific enolase, S-100, interleukin-8, or substance P endopeptidase activity.
  
  
  CONCLUSIONS
  The present study demonstrates increased concentrations of neurofilament and nociceptin in cerebrospinal fluid after nerve root compression. A simultaneous application of nucleus pulposus did not increase the response.
authors.affiliation: Department of Orthopaedics, Uppsala University Hospital, Uppsala, Sweden. michael.cornefjord@surgsci.uu.se
authors.forename: Michael
authors.initials: M
authors.lastname: Cornefjord
authors.forename: Fred
authors.initials: F
authors.lastname: Nyberg
authors.forename: Lars
authors.initials: L
authors.lastname: Rosengren
authors.forename: Helena
authors.initials: H
authors.lastname: Brisby
mesh_terms: D000818:Animals; D015415:Biomarkers; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis*; D005904:Glial Fibrillary Acidic Protein / Q000134:cerebrospinal fluid; D016209:Interleukin-8 / Q000134:cerebrospinal fluid; D007403:Intervertebral Disc / Q000737:chemistry*; D008159:Lumbar Vertebrae; D008666:Metalloendopeptidases / Q000134:cerebrospinal fluid; D009419:Nerve Tissue Proteins / Q000134:cerebrospinal fluid*; D009437:Neuralgia / Q000134:cerebrospinal fluid* / Q000209:etiology; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid; D018847:Opioid Peptides / Q000134:cerebrospinal fluid; D010751:Phosphopyruvate Hydratase / Q000134:cerebrospinal fluid; D011312:Pressure / Q000009:adverse effects; D009418:S100 Proteins / Q000134:cerebrospinal fluid; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000293:injuries*; D013314:Stress, Mechanical; D013552:Swine; D014020:Tissue Extracts / Q000494:pharmacology / Q000633:toxicity*; D000097629:Nociceptin
chemical_list: D015415:Biomarkers; D002556:Cerebrospinal Fluid Proteins; D005904:Glial Fibrillary Acidic Protein; D016209:Interleukin-8; D008666:Metalloendopeptidases; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D018847:Opioid Peptides; D010751:Phosphopyruvate Hydratase; D009418:S100 Proteins; D014020:Tissue Extracts; D000097629:Nociceptin; C029610:substance P degrading enzyme