Background: Chronic stress is a significant contributing factor to the advancement and complications of type 2 diabetes mellitus, notably the development of neuropathic pain. The amygdala, a key brain region regulating the emotional and affective aspects of pain, is susceptible to oxidative stress and inflammation. This study investigates the oxido-inflammatory changes in the amygdala and related pain behaviour in diabetic rats exposed to chronic unpredictable mild stress (CUMS) and the ameliorative effect of Sorghum bicolor polyphenol extract (SBPE).

Method: HFD/STZ-induced diabetic rats were subjected to CUMS and administered oral treatments of SBPE (200 mg/kg), metformin (250 mg/kg), or a combination of SBPE and metformin for a period of 28 days. Pain-related behaviours, inflammatory, oxidative stress and neurotransmitter-related parameters as well as histological changes in the amygdala were evaluated.

Results: Chronic stress exacerbates anxiety-like behaviour and neuropathic-like pain behaviour in diabetic rats, which was, however, reversed in SBPE and metformin-treated rats. SBPE ameliorated CUMS-induced significant elevation of TNF-α, IL-1β and myeloperoxidase in the amygdala brain tissue of diabetic rats. SBPE treatment significantly reduced malondialdehyde and nitrites and increased GSH, catalase, SOD, and GST in the amygdala. SBPE induced significant modulation of acetylcholinesterase, glutamic acid decarboxylase and arginase activities in the amygdala of diabetic rats. Distorted neuronal morphology of the amygdala in CUMS-diabetic rats was restored in SBPE-treated groups.

Conclusion: Sorghum bicolor polyphenol-rich extract relieves anxiety and neuropathic pain in chronically stressed diabetic rats possibly by inhibition of oxidative stress and inflammation in the amygdala.