Highlights
- •A galanin promoter was used to drive MOR expression in an injury-specific manner.
- •The CMV promoter was used as the control promoter in the HSV vector.
- •GalMOR-infected mice exhibited greater antinociception than cmvMOR-infected mice.
- •A greater increase in density was found in the spinal cords of galMOR-infected mice.
- •A promoter can be used to drive gene expression in an injury-specific manner.
Abstract
Chronic neuropathic pain is often difficult to treat with current pain medications.
Gene therapy is presently being explored as a therapeutic approach for the treatment
of neuropathic and cancer pain. In this study, we sought to use an injury-specific
promoter to deliver the mu-opioid receptor (MOR) transgene such that expression would
occur during the injured state only in response to release of injury-specific galanin.
To determine whether an injury-specific promoter can produce neuron-specific MOR expression
and enhanced antinociception, we compared animals infected with a galanin promoter
virus (galMOR) or a human cytomegalovirus promoter virus (cmvMOR). In behavioral assays,
we found an earlier onset and a larger magnitude of antinociception in animals infected
with galMOR compared with cmvMOR. Immunohistochemical analysis of dorsal root ganglion
neurons revealed a significant increase in MOR-positive staining in cmvMOR- and galMOR-treated
mice. Spinal cord sections from galMOR-treated mice showed a greater increase in density
but not area of MOR-positive staining. These results suggest that using injury-specific
promoters to drive gene expression in primary afferent neurons can influence the onset
and magnitude of antinociception in a rodent model of neuropathic pain and can be
used to upregulate MOR expression in populations of neurons that are potentially injury
specific.
Perspective
An injury-specific promoter (galMOR) was used to drive MOR expression in a population-
and injury-specific manner. GalMOR increased antinociception and density of MOR staining
in the spinal cord. This article presents evidence that promoter selection is an important
component in successful gene expression in an injury- and population-specific manner.
Key words
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Article info
Publication history
Published online: January 07, 2015
Accepted:
December 13,
2014
Received in revised form:
December 13,
2014
Received:
April 7,
2014
Footnotes
This work was supported by grants from the National Institutes of Health (R01 Grant NS26363), South Carolina Post Baccalaureate Research Education Program for Minorities (R25 Grants GM066526 and GM076277 from the National Institutes of Health), and Alfred P. Sloan Foundation.
The authors declare no conflicts of interest with respect to this study.
Identification
Copyright
© 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.
