Mitomycin C in preventing spinal epidural fibrosis in a laminectomy model in rats

Abstract

Object. Extensive epidural fibrosis after lumbar surgery may be the underlying cause in most cases of failed—back surgery syndrome. Various materials have been used to prevent epidural fibrosis, but only moderate success has been shown. Mitomycin C, an alkylosing antibiotic substance isolated from Streptomyces caespitosus, potentially supresses fibroblast proliferation after surgery. In this study, the authors investigated the effect of mitomycin C by local application on spinal epidural fibrosis in a rat laminectomy model. Methods. Five Wistar rats underwent laminectomy at cervical, thoracic, and lumbar levels. Based on data obtained from ophthalmological studies, mitomycin C was applied to the laminectomy sites in various concentrations (0.01, 0.05, and 0.1 mg/ml). One laminectomy site in each rat was left untreated and thus served as a control. Evoked potentials were measured pre- and postoperatively, and all rats underwent clinical evaluation. Mobility status and evidence of neurological deficit were recorded. Twelve weeks later, the rats were killed, and the spinal column, including surrounding muscle tissue, was removed en bloc, decalcified, and fixed in formaldehyde. Epidural fibrosis was evaluated histologically. In all mitomycin C—treated laminectomy sites, epidural scarring was significantly reduced compared with control sites. Remarkably, dural adhesions were absent in laminectomy defects treated with mitomycin C concentrations of 0.05 and 0.1 mg/ml. Moderate to marked epidural fibrosis with adhesion to the dura mater was noted at sites receiving 0.01 mg/ml of mitomycin C. All control sites showed dense epidural fibrosis with marked dura adherence. Conclusions. In this experimental model, mitomycin C applied locally at a concentration of 0.1 mg/ml effectively reduced epidural fibrosis, completely avoided dural adherence, and induced no side effects.