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Molecular Pain
Published in: Molecular Pain 1/2012

Open Access 01-12-2012 | Research

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

Authors: Munmun Chattopadhyay, Zhigang Zhou, Shuanglin Hao, Marina Mata, David J Fink

Published in: Molecular Pain | Issue 1/2012

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Abstract

Background

Painful neuropathy is a common complication of diabetes. Previous studies have identified significant increases in the amount of voltage gated sodium channel isoforms NaV1.7 and NaV1.3 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 NaV1.7 protein levels in DRG in vivo. To further evaluate the role of NaVα 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 NaVα subunits.

Results

Subcutaneous inoculation of the miRNA-expressing HSV vector into the feet of diabetic rats to transduce DRG resulted in a reduction in NaVα 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 NaVα 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.
Appendix
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Metadata
Title
Reduction of voltage gated sodium channel protein in DRG by vector mediated miRNA reduces pain in rats with painful diabetic neuropathy
Authors
Munmun Chattopadhyay
Zhigang Zhou
Shuanglin Hao
Marina Mata
David J Fink
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Molecular Pain / Issue 1/2012
Electronic ISSN: 1744-8069
DOI
https://doi.org/10.1186/1744-8069-8-17

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