Faculty Collaboration Database

Sustained relief of neuropathic pain by AAV-targeted expression of CBD3 peptide in rat dorsal root ganglion. Gene Ther 2014 Jan;21(1):44-51

Date

10/25/2013

Pubmed ID

24152582

Pubmed Central ID

PMC3881029

DOI

10.1038/gt.2013.56

Scopus ID

2-s2.0-84891747283 (requires institutional sign-in at Scopus site)   42 Citations

Abstract

The Ca(2+) channel-binding domain 3 (CBD3) peptide, derived from the collapsin response mediator protein 2 (CRMP-2), is a recently discovered voltage-gated Ca(2+) channel (VGCC) blocker with a preference for CaV2.2. Rodent administration of CBD3 conjugated to cell penetrating motif TAT (TAT-CBD3) has been shown to reduce pain behavior in inflammatory and neuropathic pain models. However, TAT-CBD3 analgesia has limitations, including short half-life, lack of cellular specificity and undesired potential off-site effects. We hypothesized that these issues could be addressed by expressing CBD3 encoded by high-expression vectors in primary sensory neurons. We constructed an adeno-associated viral (AAV) vector expressing recombinant fluorescent CBD3 peptide and injected it into lumbar dorsal root ganglia (DRGs) of rats before spared nerve injury (SNI). We show that selective expression of enhanced green fluorescent protein (EGFP)-CBD3 in lumbar 4 (L4) and L5 DRG neurons and their axonal projections results in effective attenuation of nerve injury-induced neuropathic pain in the SNI model. We conclude that AAV-encoded CBD3 delivered to peripheral sensory neurons through DRG injection may be a valuable approach for exploring the role of presynaptic VGCCs and long-term modulation of neurotransmission, and may also be considered for development as a gene therapy strategy to treat chronic neuropathic pain.

Author List

Fischer G, Pan B, Vilceanu D, Hogan QH, Yu H

Authors

Quinn H. Hogan MD Professor in the Anesthesiology department at Medical College of Wisconsin
Hongwei Yu MD Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Analgesics
Animals
Aptamers, Peptide
Calcium Channels, N-Type
Dependovirus
Disease Models, Animal
Ganglia, Spinal
Genetic Vectors
HEK293 Cells
Humans
Intercellular Signaling Peptides and Proteins
Lumbar Vertebrae
Male
Nerve Tissue Proteins
Neuralgia
Peptide Fragments
Rats
Rats, Sprague-Dawley
Sensory Receptor Cells