Nuclear factor-kappaB-regulated cyclooxygenase-2 expression in surgery-associated paraspinal muscle injury in rats

J Neurosurg. 2003 Mar;98(2 Suppl):181-7. doi: 10.3171/spi.2003.98.2.0181.

Abstract

Object: Paraspinal muscle injury is a common but neglected complication of posterior spinal surgery. Evidence suggests that surgical retraction places mechanical and oxidative stress on the paraspinal muscles and that inflammation is a major postoperative pathological finding in the muscles. The roles of cyclooxygenase (COX)-2 and nuclear factor (NF)-kappaB in the inflammatory processes after retraction remain to be clarified.

Methods: In the control group, paraspinal muscles were dissected from the spine via a posterior incision and then laterally retracted. Paraspinal muscle specimens were harvested before as well as at designated time points during and after persistent retraction. The time course of NF-kappaB activation was determined by gel shift assay. Expression of COX-2 was examined using Western blot analysis and immunohistochemistry. The severity of inflammation was evaluated based on histopathology and myeloperoxidase (MPO) activity. The NF-kappaB activation was inhibited by the administration of pyrrolidine dithiolcarbamate (PDTC) in the PDTC-treated group. Retraction induced early activation of NF-kappaB in paraspinal muscle cells. The expression of COX-2 could not be detected until 1 day postoperativley, reaching a peak at 3 days. The time course of COX-2 expression correlated with that of inflammatory responses and MPO activity. Pretreatment with PDTC inhibited intraoperative NF-kappaB activation and greatly downregulated postoperative COX-2 expression and inflammation in the muscles. Postinflammation fibrosis was also abolished by PDTC administration.

Conclusions: Both NF-kappaB-regulated COX-2 expression and inflammation play an important role in the pathogenesis of surgery-associated paraspinal muscle injury. The therapeutic strategy of NF-kappaB inhibition may be applicable to the prevention of such injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Collagen / metabolism
  • Cyclooxygenase 2
  • DNA / metabolism
  • Isoenzymes / metabolism*
  • Male
  • Muscle, Skeletal / injuries*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • NF-kappa B / physiology*
  • Neurosurgical Procedures / adverse effects*
  • Peroxidase / metabolism
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Spine / surgery*
  • Wounds and Injuries / etiology*
  • Wounds and Injuries / metabolism
  • Wounds and Injuries / pathology

Substances

  • Isoenzymes
  • NF-kappa B
  • Collagen
  • DNA
  • Peroxidase
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases