title: Herniated lumbar intervertebral discs spontaneously produce matrix metalloproteinases, nitric oxide, interleukin-6, and prostaglandin E2.
abstract: METHODS
  Herniated lumbar disc specimens were obtained from patients undergoing surgical discectomy for persistent radiculopathy and cultured in vitro to determine whether various biochemical agents were being produced.
  
  
  OBJECTIVE
  Our hypothesis is that biochemical mediators of inflammation and tissue degradation play a role in intervertebral disc degeneration and in the pathophysiology of radiculopathy.
  
  
  BACKGROUND
  Low back pain with or without radiculopathy is a significant clinical problem, but the etiology of low back pain and the exact pathophysiology of radiculopathy remain elusive. The biochemical events that occur with intervertebral disc degeneration and, in particular, the role of biochemical mediators of inflammation and tissue degradation have received sparse attention in the literature. There is some preliminary evidence that inflammatory mediators may have an important role in the pathophysiology of radiculopathy.
  
  
  METHODS
  Eighteen herniated lumbar discs were obtained from 15 patients undergoing disc surgery. The specimens were cultured and incubated for 72 hours, and the media were collected subsequently for biochemical analysis. Biochemical assays for matrix metalloproteinases, nitric oxide, prostaglandin E2, and a variety of cytokines were performed. As a control group, eight lumbar disc specimens were obtained from four patients undergoing anterior surgery for scoliosis and traumatic burst fractures, and similar biochemical analyses were performed.
  
  
  RESULTS
  The culture media from the herniated lumbar discs showed increased levels of matrix metalloproteinase activity compared with the control discs. Similarly, the levels of nitric oxide, prostaglandin E2, and interleukin-6 were significantly higher in the herniated discs compared with the control discs. Interleukin 1 alpha, interleukin-1 beta, tumor necrosis factor-alpha, interleukin-1 receptor antagonist protein, and substance P were not detected in the culture media of either the herniated or control discs.
  
  
  CONCLUSIONS
  Herniated lumbar discs were making spontaneously increased amounts of matrix metalloproteinases, nitric oxide, prostaglandin E2, and interleukin-6. These products may be involved intimately in the biochemistry of disc degeneration and the pathophysiology of radiculopathy. Their exact roles certainly need further investigation, but their mere presence implicates biochemical processes in intervertebral disc degeneration.
authors: Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, Pennsylvania, USA.
authors: J D
authors: JD
authors: Kang
authors: H I
authors: HI
authors: Georgescu
authors: L
authors: L
authors: McIntyre-Larkin
authors: M
authors: M
authors: Stefanovic-Racic
authors: W F
authors: WF
authors: Donaldson
authors: C H
authors: CH
authors: Evans
mesh_terms: D000328:Adult; D001857:Bone Matrix / Q000378:metabolism; D046508:Culture Techniques; D015232:Dinoprostone / Q000096:biosynthesis*; D004790:Enzyme Induction; D005260:Female; D018093:Gelatinases / Q000096:biosynthesis; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D007403:Intervertebral Disc / Q000378:metabolism; D007405:Intervertebral Disc Displacement / Q000378:metabolism* / Q000473:pathology; D008159:Lumbar Vertebrae / Q000378:metabolism*; D008297:Male; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis*; D011843:Radiculopathy / Q000473:pathology
chemical_list: D015850:Interleukin-6; D009569:Nitric Oxide; D018093:Gelatinases; D008666:Metalloendopeptidases; C030895:caseinase; D015232:Dinoprostone