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Neurochem Int. 2014 Sep;75:112-9. doi: 10.1016/j.neuint.2014.05.012. Epub 2014 Jun 2.

The role of TNF-alpha/NF-kappa B pathway on the up-regulation of voltage-gated sodium channel Nav1.7 in DRG neurons of rats with diabetic neuropathy.

Author information

1
Department of Spine Surgery, First Affiliated Hospital of Sun Yet-Sen University, Guangzhou 510080, China.
2
Department of Physiology and Pain Research Center, Zhongshan Medical School, Sun Yet-Sen University, Guangzhou 510080, China.
3
Department of Physiology, Guangzhou Medical University, Guangzhou 510182, China. Electronic address: victoria0720@126.com.

Abstract

Diabetic neuropathy (DN) is a common form of peripheral neuropathy, yet the mechanisms responsible for chronic pain in this disease are poorly understood. The up-regulation of the expression and function of voltage-gated sodium channel Nav1.7 has been implicated in DN, however, the exact mechanism is unclear. In the present study, we found that a proportion of streptozotocin (STZ)-treated rats suffered from mechanical allodynia and thermal hyperalgesia for a long-lasting time. Nav1.7 was up-regulated in spinal dorsal root ganglia (DRG) of rats with DN, double immunofluorescence staining showed that the increased Nav1.7 was co-localized with large and small sized neurons but not satellite glial cells. Inhibiting the synthesis of tumor necrosis factor-α (TNF-α) by thalidomide prevented DN, accompanied by strongly blocking the up-regulation of Nav1.7, TNF-α and p-nucleus factor-kappa B (p-NF-κB) in DRG. Intrathecal injection of NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) significantly attenuated the pain behaviors and over-expression of Nav1.7 in DRG neurons. These data suggest that increased TNF-α may be responsible for up-regulation of Nav1.7 in DRG neurons of rats with DN, and NF-κB signal pathway is involved in this process. The findings might provide potential target for preventing diabetic neuropathy.

KEYWORDS:

Diabetic neuropathy; Dorsal root ganglia; NF-κB; Sodium channel; TNF-α

PMID:
24893330
DOI:
10.1016/j.neuint.2014.05.012
[Indexed for MEDLINE]

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