title: Sodium channel Nav1.6 is up-regulated in the dorsal root ganglia in a mouse model of type 2 diabetes.
abstract: Neuropathic pain is one of the most common chronic complications of diabetes, of which the underlying mechanisms are unclear. Expression changes of voltage-gated sodium channels in dorsal root ganglia (DRG) are involved in the production of ectopic spontaneous activity. In the present study, we examined the changes of DRG Nav1.6 expression in a mouse model of type 2 diabetes (db/db mice). Db/db mice developed significant and persistent mechanical allodynia from postnatal 2 months compared to the heterozygous littermates (db/+) and C57 mice. Immunofluorescent staining showed that Nav1.6 was highly expressed in the normal DRG (approximately 31.3±5.2% of total DRG neurons), especially in the large-diameter neurons. In postnatal 5 months in db/db mice, percentage of Nav1.6 positive cells (62.9±5.5%) was significantly higher than that in C57 and db/+ mice. Western blot showed that from 2 to 5 months, Nav1.6 was increased by 1.67±0.16, 2.12±0.23, 1.89±0.32, and 2.01±0.35 folds of C57 mice, which were significantly higher than that of the C57 and db/+ mice. Real-time PCR showed that in postnatal 1 month of db/db mice, mRNA level of Nav1.6 was increased by 1.72±0.22 fold, which was significantly higher than that of C57 and db/+ mice. Nav1.6 mRNA was increased thereafter and maintained at high levels throughout the observed period. Our results provide direct evidence that type 2 diabetes induces significant and persistent increase of Nav1.6 expression in the DRG, which may participate in the diabetic neuropathic pain.
authors.affiliation: Department of Hepatobiliary Surgery, Lanzhou Military Region General Hospital, Lanzhou, China.
authors.forename: Yan-Shun
authors.initials: YS
authors.lastname: Ren
authors.forename: Nian-Song
authors.initials: NS
authors.lastname: Qian
authors.forename: Yu
authors.initials: Y
authors.lastname: Tang
authors.forename: Yong-Hui
authors.initials: YH
authors.lastname: Liao
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Yang
authors.forename: Ke-Feng
authors.initials: KF
authors.lastname: Dou
authors.forename: Masakazu
authors.initials: M
authors.lastname: Toi
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism*; D006930:Hyperalgesia / Q000503:physiopathology; D008124:Locomotion / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011975:Receptors, Mitogen / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011975:Receptors, Mitogen; C491046:Scn8a protein, mouse; D015222:Sodium Channels