Effects of tramadol and levetiracetam in preventing peridural fibrosis after laminectomy in rats
Neurological Research, cilt.48, sa.5, ss.620-636, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 48 Sayı: 5
- Basım Tarihi: 2026
- Doi Numarası: 10.1080/01616412.2025.2538130
- Dergi Adı: Neurological Research
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS
- Sayfa Sayıları: ss.620-636
- Anahtar Kelimeler: inflammation, levetiracetam, methylprednisolone, Peridural fibrosis, tramadol
- Ankara Yıldırım Beyazıt Üniversitesi Adresli: Evet
Özet
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-β, 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.