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Painful neuropathy is a frequent comorbidity in diabetes. Zucker diabetic fatty (ZDF, fa/fa) rats develop type 2 diabetes spontaneously with ageing and show nociceptive hypersensitivity by age of 13wk. In preclinical and clinical studies, the treatment of diabetic neuropathy is challenging but complementary medicine like transcutaneous auricular vagus nerve stimulation (taVNS) appears beneficial to the relief of neuropathic pain. However, the mechanism behind the effectiveness of taVNS remains unclear. In this study we show that daily 30min taVNS (2/15Hz, 2mA) for consecutive 27 days effectively inhibited the development of nociceptive hypersensitivity in ZDF rats as detected by thermal hyperalgesia and mechanical allodynia in hindpaw. We also demonstrated that this beneficial effect in nociceptive behavior is related to an elevated serotonin (5-HT) plasma concentration and an upregulated expression of 5-HT receptor type 1A (5-HT1AR) in hypothalamus. We conclude that daily 30min taVNS sessions lessen diabetic neuropathy development by enhancing serotonergic function in genetically diabetes prone individuals.

Auricular vagus nerve stimulation enhances central serotonergic function and inhibits diabetic neuropathy development in Zucker fatty rats