糖尿病前期
神经病理性疼痛
背根神经节
下调和上调
痛觉过敏
化学
药理学
神经科学
医学
内科学
内分泌学
糖尿病
感觉系统
生物
受体
伤害
生物化学
2型糖尿病
基因
作者
Wei Sun,Fan Yang,Yan Wang,Yan Yang,Rui Du,Xiao‐Liang Wang,Zheng Luo,Junmei Wu,J. Chen
标识
DOI:10.1002/advs.202310295
摘要
Abstract Neuropathic pain can occur during the prediabetic stage, even in the absence of hyperglycemia. The presence of prediabetic neuropathic pain (PDNP) poses challenges to the management of individuals with prediabetes. However, the mechanisms underlying this pain remain unclear. This study aims to investigate the underlying mechanism and identify potential therapeutic targets of PDNP. A prediabetic animal model induced by a high‐energy diet exhibits both mechanical allodynia and thermal hyperalgesia. Furthermore, hyperexcitability and decreased potassium currents are observed in the dorsal root ganglion (DRG) neurons of these rats. TREK1 and TREK2 channels, which belong to the two‐pore‐domain K + channel ( K 2P ) family and play an important role in controlling cellular excitability, are downregulated in DRG neurons. Moreover, this alteration is modulated by Sortilin, a molecular partner that modulates the expression of TREK1. The overexpression of Sortilin negatively affects the expression of TREK1 and TREK2, leading to increased neuronal excitability in the DRG and enhanced peripheral pain sensitivity in rats. Moreover, the downregulation of Sortilin or activation of TREK1 and TREK2 channels by genetic or pharmacological approaches can alleviate PDNP. Therefore, targeting the Sortilin‐mediated TREK1/2 pathway may provide a therapeutic approach for ameliorating PDNP.
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