Alpha-lipoic acid downregulates TRPV1 receptor via NF-κB and attenuates neuropathic pain in rats with diabetes

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Abstract

Aims: Painful diabetic neuropathy (PDN) is a refractory complication of diabetes. The study aimed to investigate the role of α-lipoic acid (ALA) on the regulation of transient receptor potential vanilloid-1 (TRPV1) in dorsal root ganglion (DRG) neurons of rats with diabetes. Methods: Whole-cell patch-clamp recordings were employed to measure neuronal excitability in DiI-labeled DRG neurons of control and streptozotocin (STZ)-induced diabetic rats. Western blotting and immunofluorescence assays were used to determine the expression and location of NF-κBp65 and TRPV1. Results: STZ-induced hindpaw pain hypersensitivity and neuronal excitability in L4-6 DRG neurons were attenuated by intraperitoneal injection with ALA once a day lasted for one week. TRPV1 expression was enhanced in L4-6 DRGs of diabetic rats compared with age-matched control rats, which was also suppressed by ALA treatment. In addition, TRPV1 and p65 colocated in the same DRG neurons. The expression of p65 was upregulated in L4-6 DRGs of diabetic rats. Inhibition of p65 signaling using recombinant lentiviral vectors designated as LV-NF-κBp65 siRNA remarkably suppressed TRPV1 expression. Finally, p65 expression was downregulated by ALA treatment. Conclusion: Our findings demonstrated that ALA may alleviate neuropathic pain in diabetes by regulating TRPV1 expression via affecting NF-κB.

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Zhang, B. Y., Zhang, Y. L., Sun, Q., Zhang, P. A., Wang, X. X., Xu, G. Y., … Zhang, H. H. (2020). Alpha-lipoic acid downregulates TRPV1 receptor via NF-κB and attenuates neuropathic pain in rats with diabetes. CNS Neuroscience and Therapeutics, 26(7), 762–772. https://doi.org/10.1111/cns.13303

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