Pregabalin as a neuroprotective alternative to methylprednisolone in peripheral nerve regeneration: an experimental study

Background Peripheral nerve injuries are particularly important in terms of their frequency and complications. The purpose of this experimental study was to investigate the neuroprotective effects of pregabalin and methylprednisolone administered at different doses and in combination in an axonotmesis model and to establish whether pregabalin can represent an alternative to methylprednisolone. Methods Fifty-six adult male Sprague-Dawley rats were assigned to control, sham (axonotmesis only), axonotmesis + pregabalin 30 mg/kg (low dose), axonotmesis + pregabalin 60 mg/kg (high dose), axsonotmezis + 1 mg/kg methylprednisolone, axonotmesis + pregabalin 30 mg/kg + 1 mg/kg methylprednisolone (low-dose combination), and axonotmesis + pregabalin 60 mg/kg + 1 mg/kg methylprednisolone (high-dose combination) groups. Following axonotmesis, the treatment groups received oral treatment once daily for one week. Sciatic functional index, electromyography, biochemical (NGF, TGF-β, CNTF, MBP), immunohistochemical, histomorphological and immunofluorescence analyses were performed to assess the neuroprotective effects of the treatments. Results Immunohistochemical, electrophysiological, and biochemical analyses demonstrated that the separate or combined use of pregabalin and methylprednisolone may have positive effects on nerve regeneration. Conclusion Low-dose pregabalin and methylprednisolone alone exhibited similar effects on peripheral nerve regeneration and functional healing. Pregabalin may represent an alternative to steroids due to its fewer side effects. Although direct pain behavior assessment was not performed in this study, the effect of pregabalin on neuropathic pain may be additionally beneficial in combined use. These results demonstrate that pregabalin offers comparable neuroregenerative effects to methylprednisolone, with combination therapy proving superior. This positions pregabalin as a promising steroid-sparing agent for peripheral nerve injury, warranting further clinical investigation. © 2025 HCFMUSP.