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

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)-κB 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-κB 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-κB activation was inhibited by the administration of pyrrolidine dithiolcarbamate (PDTC) in the PDTC-treated group. Retraction induced early activation of NF-κB 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-κB activation and greatly downregulated postoperative COX-2 expression and inflammation in the muscles. Postinflammation fibrosis was also abolished by PDTC administration. Conclusions. Both NF-κB-regulated COX-2 expression and inflammation play an important role in the pathogenesis of surgery-associated paraspinal muscle injury. The therapeutic strategy of NF-κB inhibition may be applicable to the prevention of such injury.