Use of pimecrolimus to prevent epidural fibrosis in a postlaminectomy rat model

J Neurosurg Spine. 2009 Dec;11(6):758-63. doi: 10.3171/2009.6.SPINE08580.

Abstract

Object: Epidural fibrosis is the scar tissue formed over the dura mater after a laminectomy. Extensive epidural fibrosis may be an important underlying cause of failed back syndrome. Pimecrolimus, an ascomycin derivative, is one of the new classes of immunomodulating macrolactams and was specifically developed for the treatment of inflammatory diseases. This study examined the preventive effects of the local application of pimecrolimus in minimizing spinal epidural fibrosis in a rat laminectomy model.

Methods: Thirty Wistar rats were divided into 3 equal groups: control, mitomycin C (MMC), and pimecrolimus groups. Each rat underwent a laminectomy at the L-3 lumbar level. In the experimental groups, a cotton pad soaked with MMC (0.5 mg/ml) or 5 mg pimecrolimus was placed on the exposed dura mater. No treatment was performed in the control group rats. Thirty days after surgery, the rats were killed and the dura mater thickness, epidural fibrosis, and arachnoidal involvement were quantified.

Results: The mean dura thickness was measured at 9.28 +/- 3.39 microm in the MMC group and at 8.69 +/- 2.32 microm in the pimecrolimus group, compared with 14.70 +/- 4.14 microm in the control group. In addition, the epidural fibrosis and arachnoidal involvement were reduced significantly in the treatment groups compared with the control group.

Conclusions: In this animal model, it was shown that locally applied pimecrolimus effectively reduces epidural fibrosis and dural adherence in rats that underwent lumbar laminectomy. Mitomycin C was equally effective as pimecrolimus in reducing epidural fibrosis and dural adherence in this study.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Chi-Square Distribution
  • Dura Mater / pathology*
  • Fibrosis / pathology
  • Fibrosis / prevention & control
  • Laminectomy*
  • Male
  • Mitomycin / pharmacology
  • Photomicrography
  • Rats
  • Rats, Wistar
  • Statistics, Nonparametric
  • Tacrolimus / analogs & derivatives*
  • Tacrolimus / pharmacology
  • Tissue Adhesions / pathology
  • Tissue Adhesions / prevention & control

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Mitomycin
  • pimecrolimus
  • Tacrolimus