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. 2025 Apr 8;16:1480534. doi: 10.3389/fimmu.2025.1480534

Table 2.

Mechanisms of ion channel regulation in diabetic neuropathic pain.

Ion Channel Year Intervention Model Mechanism References
Sodium Channel 2019 / STZ Model Upregulation of NaV1.7, increased total sodium current, TTXs sodium current, and TTXr sodium current density (114)
Sodium Channel 2015 Curcumin HFD Model Inhibition of current density and TTX-R sodium currents in small-sized DRG neurons (115)
Sodium Channel 2011 / db/db/db/+ Increase in Nav1.6 protein and mRNA expression; increase in Nav1.6 positive cells proportion (116)
Sodium Channel 2004 / STZ Model Decrease in the expression of Na(v)1.6 (TTX-S) and Na(v)1.8 (TTX-R), increase in tyrosine phosphorylation of Na(v)1.6 and Na(v)1.7, significant increase in both TTX-S and TTX-R sodium currents in small DRG neurons isolated from diabetic rats (110)
Sodium Channel 2015 AAV-shRNA-Nav1.3 STZ Model Downregulation of expression of Nav1.3, reduced neuronal excitability of dorsal horn neurons (117)
Sodium Channel 2012 / STZ Model Upregulation of expression of Nav1.7 and Nav1.8; enhancement of transient and persistent sodium currents, increase in neuronal excitability (106)
Potassium Channel 2024 Branched-Chain Amino Acids HFD/STZ/db/db Model Activation of expression of L-type amino acid transporter 1 (LAT1), decreased localization of Kv1.2 on the cell membrane, inhibition of Kv1.2 channels, increased neuronal excitability (118)
Potassium Channel 2015 α-dendrotoxin (α-DTX) STZ Model Reduction in conduction failure of C-fibers; decrease in expression of Kv1.2 and Kv1.6 (119)
Potassium Channel 2018 / STZ Model Significant reduction in mRNA and protein levels of KCNQ/3/5 channels, decreased IM density, increased excitability of DRG neurons (120)
Potassium Channel 2010 / STZ Model Marked reduction in densities of total Kv, A-type (IA), and sustained delayed (IK) currents in medium- and large-, but not in small-diameter DRG neurons (121)
Calcium Channel 2022 / STZ/db/db Model Activation of GPR77 receptor mediates WNT5a release followed by activation of TRPV1 channel, induction of rapid currents (99)
Calcium Channel 2022 / STZ Model Activation of PKCϵ/P38 MAPK/NF-κB signaling pathway increases TRPV1 expression (122)
Calcium Channel 2023 Selenium, Curcumin STZ Model Reduction in mean densities of TRPM7 currents, increase in calcium concentration (123)
Calcium Channel 2023 Alpha-lipoic acid STZ Model Reduction in TRPV1 current density and intracellular free Ca2+ concentration (124)
Calcium Channel 2023 Alpha-lipoic acid STZ Model Inhibition of TRPV4 channel, reduction in intracellular free Ca2+ concentration (125)
Calcium Channel 2017 Melatonin, Selenium STZ Model Reduction in current densities of TRPM2 and TRPV1 channels, decreased intracellular free Ca^2+ concentration (126)