DefinePK

Abstract

Background: Increased nociceptive sensitivity and neuroinflammation are hallmarks of peripheral neuropathic pain (PNP), a chronic and incapacitating condition brought on by nerve damage or metabolic abnormalities. Rats' chronic constriction injury (CCI) model accurately mimics human PNP. Natural antioxidants ferulic acid (FA) and alpha-lipoic acid (ALA) have strong anti-inflammatory and neuroprotective effects. In a CCI-induced PNP model in rats, this study examined and contrasted the therapeutic potential of ALA, FA, and their combination with the common medication gabapentin.
Methods: Five groups (n=6) of adult Wistar rats were created: Disease Control, Gabapentin (30 mg/kg, i.p.), alpha-lipoic acid (25 mg/kg, p.o.), ferulic acid (10 mg/kg, p.o.), and a combination of alpha-lipoic acid + ferulic acid (12 mg/kg + 5 mg/kg, p.o.). Mechanical allodynia (von Frey), cold allodynia (acetone), thermal hyperalgesia (hot plate), and mechanical hyperalgesia (pinprick) tests were among the behavioural evaluations. In sciatic nerve homogenates, biochemical analyses determined the levels of SOD, CAT, GSH, MDA, and TNF-α. Axonal integrity and inflammation were evaluated by histopathological analysis.
Results: Pro-inflammatory markers, oxidative stress, and nociceptive behaviour were all markedly elevated by CCI. ALA or FA monotherapy produced modest gains. However, their combined effects closely mirrored those of gabapentin, significantly reducing pain behaviour and normalising oxidative and inflammatory parameters. Better axonal preservation in combination-treated rats was confirmed by histology.
Conclusion: The synergistic neuroprotective and antioxidant effects of ALA and FA, particularly when combined, point to their potential as an adjuvant or alternative therapy for management of PNP.