Examining the effectiveness of nintedanib in preventing post-laminectomy epidural fibrosis in rats

In this rat model study, we examined the effects of topical and systemic nintedanib treatment on the development of post-laminectomy epidural fibrosis.

Thirty-two rats were divided into four equal groups (n=8 per group). An L1-L2 laminectomy was performed using standard microsurgical procedures. The control group underwent laminectomy only; the sterile saline group underwent laminectomy followed by sterile saline irrigation; the topical nintedanib group underwent laminectomy followed by topical nintedanib application; and the systemic nintedanib group underwent laminectomy followed by oral nintedanib administration. The degree of fibrosis was evaluated by histological examination. Plasma levels of matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), transforming growth factor beta-1 (TGF-β1), tumor necrosis factor-alpha (TNF-α), hydroxyproline (HYP), and myeloperoxidase (MPO) were compared among the groups.

In the control group, two rats developed grade 2 epidural fibrosis, while six animals developed grade 3 fibrosis. The sterile saline group demonstrated a similar degree of fibrosis to the control group. In the topical nintedanib group, three, four, and one rat developed grade 1, grade 2, and grade 3 epidural fibrosis, respectively. In the systemic nintedanib group, five rats had grade 1 epidural fibrosis, whereas three rats had grade 2 fibrosis. Groups 3 and 4 showed significantly decreased plasma levels of MMP-9, IL-6, VEGF, TGF-β1, TNF-α, and HYP compared to Groups 1 and 2 (p<0.05). Plasma levels of these markers were lower in Group 4 than in Group 3; however, the difference was not statistically significant (p>0.05). Plasma MPO activity in the study groups was not altered following nintedanib treatment (p>0.05).

The histological and biochemical findings of the present study indicate that nintedanib is a promising pharmacological agent for the prevention of post-laminectomy epidural fibrosis. Further studies with larger sample sizes and interval assessments are needed to clarify the effects of different dosages.