Reduction of voltage gated sodium channel protein in DRG by vector mediated miRNA reduces pain in rats with painful diabetic neuropathy

Molecular Pain

David J Fink¹  Marina Mata²  Shuanglin Hao⁴  Zhigang Zhou³  Munmun Chattopadhyay² 

[1] 1500 E Medical Center Drive, Ann Arbor, MI 48109, USA;Department of Neurology, University of Michigan and VA Ann Arbor Healthcare System, Ann Arbor, MI, USA;Department of Pathology, University of North Carolina, Chapel Hill, NC, USA;Department of Anesthesiology, University of Miami, Miami, FL, USA

关键词: Sodium channel;    Gene therapy;    Neuropathy;    Pain;    Diabetes;   

Others  :  865499
DOI  :  10.1186/1744-8069-8-17

 received in 2011-12-09, accepted in 2012-03-22,  发布年份 2012

【 摘 要 】

Background

Painful neuropathy is a common complication of diabetes. Previous studies have identified significant increases in the amount of voltage gated sodium channel isoforms Na_V1.7 and Na_V1.3 protein in the dorsal root ganglia (DRG) of rats with streptozotocin (STZ)-induced diabetes. We found that gene transfer-mediated release of the inhibitory neurotransmitters enkephalin or gamma amino butyric acid (GABA) from DRG neurons in diabetic animals reduced pain-related behaviors coincident with a reduction in Na_V1.7 protein levels in DRG in vivo. To further evaluate the role of Na_Vα subunit levels in DRG in the pathogenesis of pain in diabetic neuropathy, we constructed a non-replicating herpes simplex virus (HSV)-based vector expressing a microRNA (miRNA) against Na_Vα subunits.

Results

Subcutaneous inoculation of the miRNA-expressing HSV vector into the feet of diabetic rats to transduce DRG resulted in a reduction in Na_Vα subunit levels in DRG neurons, coincident with a reduction in cold allodynia, thermal hyperalgesia and mechanical hyperalgesia.

Conclusions

These data support the role of increased Na_Vα protein in DRG in the pathogenesis of pain in diabetic neuropathy, and provide a proof-of-principle demonstration for the development of a novel therapy that could be used to treat intractable pain in patients with diabetic neuropathy.

【 授权许可】

   
2012 Chattopadhyay et al; licensee BioMed Central Ltd.

【 图 表 】

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