title: 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.
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.
authors.affiliation: Department of Spine Surgery, First Affiliated Hospital of Sun Yet-Sen University, Guangzhou 510080, China.
authors.forename: Yangliang
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Physiology and Pain Research Center, Zhongshan Medical School, Sun Yet-Sen University, Guangzhou 510080, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zang
authors.affiliation: Department of Physiology and Pain Research Center, Zhongshan Medical School, Sun Yet-Sen University, Guangzhou 510080, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Physiology and Pain Research Center, Zhongshan Medical School, Sun Yet-Sen University, Guangzhou 510080, China.
authors.forename: Wenshan
authors.initials: W
authors.lastname: Gui
authors.affiliation: Department of Physiology and Pain Research Center, Zhongshan Medical School, Sun Yet-Sen University, Guangzhou 510080, China.
authors.forename: Xianguo
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Physiology, Guangzhou Medical University, Guangzhou 510182, China. Electronic address: victoria0720@126.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhong
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003929:Diabetic Neuropathies / Q000503:physiopathology*; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D062556:NAV1.7 Voltage-Gated Sodium Channel / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D013792:Thalidomide / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D062556:NAV1.7 Voltage-Gated Sodium Channel; D016328:NF-kappa B; C503480:Scn9a protein, rat; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide; D013311:Streptozocin
keywords: Diabetic neuropathy; Dorsal root ganglia; NF-κB; Sodium channel; TNF-α