Effects of tramadol and levetiracetam in preventing peridural fibrosis after laminectomy in rats.

Abstract

Objective: This study examined the therapeutic effects of tramadol hydrochloride and levetiracetam on preventing peridural fibrosis after laminectomy in rats.

Methods: Under sedation anesthesia, standard laminectomies at T9, T10, and T11 were performed on 32 male Wistar albino rats weighing 300-350 g. The rats were then divided into groups: Sham (no pharmacological agent administered, n = 6 + 2); MP group (10 mg/kg/day methylprednisolone sodium succinate administered intraperitoneally for 14 days, n = 6 + 2); TRA group (0.6 mg/kg/day tramadol hydrochloride administered intraperitoneally for 14 days, n = 6 + 2); and LEV group (15 mg/kg/day levetiracetam administered intraperitoneally for 14 days, n = 6 + 2). Four weeks after surgery, all animals were euthanized, and their spinal columns were removed en bloc. Peridural fibrosis and collagen density were evaluated using hematoxylin-eosin and Masson-Trichrome staining, respectively. Collagen and alpha-SMA levels were assessed with COL1A1 and ACTA2 staining, respectively. ELISA measurements were taken for TNF-α, IL-6, TGF-ß, CTGF, caspase-3, and GSH/GSSG levels. Western blot analysis was performed to determine pAMPK, mTOR, pmTOR, and mTOR/p-mTOR levels.

Results: Histopathological and immunohistochemical analyses showed that methylprednisolone and tramadol reduced peridural fibrosis, collagen density, and collagen formation. Both agents exhibited anti-inflammatory and anti-apoptotic effects by decreasing TNF-α, IL-6, caspase-3, TGF-β, and CTGF levels. They demonstrated antioxidant properties by increasing GSH/GSSG levels, and they supported autophagy by increasing pAMPK and decreasing pmTOR levels.

Conclusion: In summary, all three agents possessed anti-inflammatory, antioxidant, anti-apoptotic, and autophagy-associated tissue regenerative properties. Due to these effects, they have the potential to reduce peridural fibrosis in the rat laminectomy model.