Diabetic neuropathic pain (DNP) is a common, complex, and severe complication of diabetes. It can lead to increased mortality, lower-limb amputations, and distressing neuropathic symptoms. Available therapies for DNP are broad-spectrum analgesics, related to various side effects. Transient receptor potential vanilloid-1 (TRPV1) is widely expressed within the peripheral and central nervous systems and plays an essential role in pain perception and regulation. Both TRPV1 agonists and antagonists could reduce the sensitivity to nociception. Some exhibit blood glucose homeostasis regulates function by influencing insulin secretion and receptor sensitivity. Since TRPV1 has exhibited the unique advantages of simultaneously managing blood sugar and pain, developing new TRPV1 channel modulators for diabetes-related pain syndrome is a promising alternative to conventional therapy. In this review, the role of TRPV1 in the pathogenesis of DNP has been described and challenges of TRPV1 modulators have been explored to be a new therapy for DNP.
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