Objective: To determine the effects of fisetin and alpha lipoic acid (ALA) on diabetic neuropathic pain development and their acute and chronic effects on established neuropathic pain in vivo, in an experimental mice model.

Materials and Methods: Type I diabetes mellitus was induced by streptozotocin (STZ, 150 mg/kg, i.p.) in adult male BALB/C mice. After confirmation of diabetes, animals were divided into two main groups: acute and chronic. The chronic group had three subgroups; control (no treatment), fisetin (10 mg/kg, i.p.) and ALA (10 mg/kg) groups (n=9 for each). Fisetin and ALA treatment was started at 3th week following STZ injection and applied weekly for the next 5 weeks. Pain threshold, as measured by paw withdrawal latency in response to heat stimulus, was measured by plantar analgesiometer at baseline and just before the consecutive injection time points. The acute group had further subgroups including control, fisetin (3 and 10 mg/kg), ALA (50 and 100 mg/kg) and combination group (Fisetin 5 mg/kg and ALA 10 mg/kg). In acute tests pain threshold measurements were performed at 10, 30, 60 and 90 minutes.

Results: Chronic treatment with ALA and fisetin prevented neuropathic hyperalgesia development. Acute application of ALA provided dose and time dependent analgesic effect. Acute fisetin application did not provide analgesia but in combination it contributed analgesic actions of ALA.

Conclusion: Both chronic ALA and fisetin treatment effectively prevented neuropathic pain development. Acute test on established neuropathic pain revealed that ALA was more effective than fisetin in ameloriating hypoalgesia in this study.