Changes of sodium channel expression in experimental painful diabetic neuropathy.
Although pain is experienced by many patients with diabetic neuropathy, the pathophysiology of painful diabetic neuropathy is not understood. Substantial evidence indicates that dysregulated sodium channel gene transcription contributes to hyperexcitability of dorsal root ganglion neurons, which may produce neuropathic pain after axonal transection. In this study, we examined sodium channel mRNA and protein expression in dorsal root ganglion neurons in rats with streptozotocin-induced diabetes and tactile allodynia, using in situ hybridization and immunocytochemistry for sodium channels Na(v)1.1, Na(v)1.3, Na(v)1.6, Na(v)1.7, Na(v)1.8, and Na(v)1.9. Our results show that, in rats with experimental diabetes, there is a significant upregulation of mRNA for the Na(v)1.3, Na(v)1.6, and Na(v)1.9 sodium channels and a downregulation of Na(v)1.8 mRNA 1 and 8 weeks after onset of allodynia. Channel protein levels display parallel changes. Our results demonstrate dysregulated expression of the genes for sodium channels Na(v)1.3, Na(v)1.6, Na(v)1.8, and Na(v)1.9 in dorsal root ganglion neurons in experimental diabetes and suggest that misexpression of sodium channels contributes to neuropathic pain associated with diabetic neuropathy.
Craner
Matthew J
MJ
Department of Neurology, Paralyzed Veterans of America/Eastern Paralyzed Veterans Association Center for Neuroscience and Regeneration Research, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
Klein
Joshua P
JP
Renganathan
Muthukrishnan
M
Black
Joel A
JA
Waxman
Stephen G
SG
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism*; D003929:Diabetic Neuropathies / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000096:biosynthesis*
D012333:RNA, Messenger; D015222:Sodium Channels