Effects of sodium-2-mercaptoethanesulfonate on perineural fibrosis and inflammation secondary to peripheral nerve surgery in rats

Objectives: This study evaluated whether topical sodium 2-mercaptoethanesulfonate (Mesna) reduces perineural adhesion, fibrosis, and chronic inflammation after sciatic nerve dissection in rats. Methods: Twenty-one adult male Wistar rats were randomized to baseline histological reference, saline vehicle, or Mesna groups ( n = 7/group). The right sciatic nerve was exposed and dissected free from surrounding tissues. In the baseline group, a 1-cm nerve segment with surrounding perineural tissue was excised during initial surgery. In the other groups, 2 mL normal saline or 100 mg Mesna diluted in 2 mL saline was applied topically to the dissection site. These animals underwent re-exploration at 4 weeks. Macroscopic adhesion was graded using the Rydell classification; fibrosis and chronic inflammation were assessed blindly on hematoxylin and eosin (H&E) and Masson’s trichrome-stained sections. Results: Median (interquartile range) Rydell scores were lower with Mesna than with saline (1.0 [1.0–1.5] versus 3.0 [2.5–3.0]; p = 0.0035). Fibrosis scores were also lower with Mesna on H&E (1.0 versus 4.0; adjusted p = 0.0023) and Masson’s trichrome (1.0 versus 4.0; adjusted p = 0.0017), as were chronic inflammation scores (2.0 versus 3.0; adjusted p = 0.0326 and 1.0 versus 3.0; adjusted p = 0.0117, respectively). Histological abnormalities were not completely eliminated relative to baseline. Conclusion: A single topical dose of Mesna attenuated perineural adhesion, fibrosis, and chronic inflammation 4 weeks after sciatic nerve dissection. Further dose-response and long-term functional and electrophysiological studies are needed to clarify neural safety and clinical relevance.