Metformin attenuates post-epidural fibrosis by inhibiting the TGF-ß1/Smad3 and HMGB1/TLR4 signaling pathways.

Excessive post-epidural fibrosis is a common cause of recurrent back pain after spinal surgery. Though various treatment methods have been conducted, the safe and effective drug for alleviating post-epidural fibrosis remains largely unknown. Metformin, a medicine used in the treatment of type 2 diabetes, has been noted to relieve fibrosis in various organs. In the present study, we aimed to explore the roles and mechanisms of metformin in scar formation in a mouse model of laminectomy. Post-epidural fibrosis developed in a mouse model of laminectomy by spinous process and the T12-L2 vertebral plate with a rongeur. With the administration of metformin, post-epidural fibrosis was reduced, accompanied with decreased collagen and fibronectin in the scar tissues. Mechanistically, metformin decreased fibronectin and collagen deposition in fibroblast cells, and this effect was dependent on the HMGB1/TLR4 and TGF-ß1/Smad3 signalling pathways. In addition, metformin influenced the metabolomics of the fibroblast cells. Taken together, our study suggests that metformin may be a potential option to mitigate epidural fibrosis after laminectomy.

Narcotic Addiction in Failed Back Surgery Syndrome.

Back pain is a common health problem that reduces the quality of life for human beings worldwide. Several treatment modalities have been reported as effective for pain relief. Generally, patients often undergo surgical interventions as pain becomes intractable, after conservative treatment. With advances in surgical techniques, those choosing spinal surgery as an option have increased over time, and instrumentation is more popular than it was years ago. However, some patients still have back pain after spinal operations. The number of patients classified as having failed back surgery syndrome (FBSS) has increased over time as has the requirement for patients receiving long-term analgesics. Because pain relief is regarded as a human right, narcotics were prescribed more frequently than before. Narcotic addiction in patients with FBSS has become an important issue. Here, we review the prevalence of FBSS, the mechanism of narcotic addiction, and their correlations. Additionally, several potentially effective strategies for the prevention and treatment of narcotic addiction in FBSS patients are evaluated and discussed.

Alpha-lipoic acid inhibits peridural fibrosis following laminectomy through the inactivation of TGF-ß1, PDGF, PAI-1 and IL-6 expressions.

AIM: The objective of this study was to investigate the antifibrotic effect of parenteral administration of alpha-lipoic acid (ALA), which has been reported to reduce fibrosis in the liver, oral mucosa, and peritoneum, in laminectomized rabbits as a potential candidate for the prevention of peridural fibrosis. MATERIAL AND METHODS: Twelve adult New Zealand white male rabbits were divided into control (n=6) and ALA treatment groups (n=6). Laminectomy of the lumbar spine was performed in all animals, and ALA was administered intramuscularly in six rabbits composing the treatment group. Total RNA obtained from the paraffin-embedded tissues was analyzed for transforming growth factor-ß1 (TGF-ß1), plateletderived growth factor (PDGF), plasminogen activator inhibitor-1 (PAI-1) and interleukin-6 (IL-6). RESULTS: mRNA investigations showed that TGF-ß1, PDGF, PAI-1 and IL-6 gene expressions, which constitute strong evidence for the development of fibrosis, were significantly lower in the treatment group compared with the results obtained from the control group. According to the histological peridural grading, the ALA-treated group showed significantly less peridural fibrosis than the control group. CONCLUSION: Intramuscular administration of ALA is a promising treatment for the prevention of peridural fibrosis in the postoperative period.