Background and purpose: Neuropathy is one of the common complications of diabetes mellitus. This study aimed to determine the analgesic and antiapoptotic effects of the aqueous extract of Achillea millefolium L. (Ach) in rats with experimental painful diabetic neuropathy by behavioral and molecular procedures. Experimental approach: Thirty male Wistar rats were divided into 5 groups including control, diabetes + saline, and diabetes + Ach extract (doses of 150, 300, and 600 mg/kg/day for 3 weeks, orally). A tail-flick test was performed to assess the pain threshold in different groups. Western blotting test was used to evaluate the apoptotic (Bax, Bcl2, cleaved caspase-3, and cytochrome-c) and inflammatory (TNF-α and NF-kB) protein factors in the lumbar portion of the spinal cord tissue. Also, commercial assay kits were used to evaluate oxidative stress factors (MDA, GPx, and SOD enzyme activity) in the lumbar portion of the spinal cord tissue. Findings/Results: Results showed that administering Ach extract at the doses of 300 and 600 mg/kg/day significantly increased the nociception threshold in treated diabetic animals compared to untreated diabetic animals. Moreover, the treatment of diabetic animals with Ach extract (300 and 600 mg/kg/day) significantly reduced the oxidative stress, inflammation, and apoptosis biochemical indicators in the lumbar spinal cord tissue compared to the untreated diabetic group. Conclusion and implications: The findings showed that Ach extract has neuroprotective and anti-nociceptive effects in rats with diabetic neuropathy. The effects can be due to the inhibition of oxidative stress, inflammation, and apoptosis in the spinal cord tissue.
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