Abstract
Study design
This is an animal study.
Objectives
Metformin is a safe drug for controlling blood sugar in diabetes. It has been shown that metformin improves locomotor recovery after spinal cord injury (SCI). Neuropathic pain is also a disturbing component of SCI. It is indicated that metformin has neuroprotective and anti-inflammatory effects, which attenuate neuropathic pain and hyperalgesia in injured nerves. Thus, we evaluated metformin’s therapeutic effects on SCI neuroinflammation and its sensory and locomotor complications. Meanwhile, results were compared to minocycline, an anti-neuroinflammation therapy in SCI.
Setting
Experimental Medicine Research Center, Tehran University of Medical Sciences, Iran
Methods
In an animal model of SCI, 48 male rats were subjected to T9 vertebra laminectomy. Animals were divided into a SHAM-operated group and five treatment groups. The treatments included normal saline as a vehicle control group, minocycline 90 mg/kg and metformin at the doses of 10, 50 and 100 mg/kg. Locomotor scaling, behavioral tests for neuropathic pain and weight changes were evaluated and compared through a 28-days period. At the end of the study, tissue samples were taken to assess neuroinflammatory changes.
Results
Metformin 50 mg/kg improved the locomotors ability (p < 0.001) and decreased sensitivity to mechanical and thermal allodynia (p < 0.01). These results were compatible with minocycline effect on SCI (p > 0.05). While metformin led to weight loss, both metformin and minocycline significantly decreased neuroinflammation in the assessment of cord tissue histopathology, and levels of TNF-α and interleukin-1β (p < 0.001).
Conclusions
Metformin could be considered as an alternative therapeutic agent for SCI, as it potentially attenuates neuroinflammation, sensory and locomotor complications of cord injury.
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Acknowledgements
This study was financially supported by Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran (Grant No 95-01-30-31469) and by a grant (96002757) from the Iran National Science Foundation (INSF). We gratefully acknowledge the dedicated efforts of the investigators including Dr. Mohsen Afarideh and the coordinators who participated in this study.
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Afshari, K., Dehdashtian, A., Haddadi, NS. et al. Anti-inflammatory effects of Metformin improve the neuropathic pain and locomotor activity in spinal cord injured rats: introduction of an alternative therapy. Spinal Cord 56, 1032–1041 (2018). https://doi.org/10.1038/s41393-018-0168-x
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DOI: https://doi.org/10.1038/s41393-018-0168-x
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