Injury-specific promoters enhance herpes simplex virus-mediated gene therapy for treating neuropathic pain in rodents

Sherika N. Smith, Candler Paige, Kandy T. Velazquez, Terika P. Smith, Srinivasa Naga Raja, Steven P. Wilson, Sarah M. Sweitzer

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)283-290
Number of pages8
JournalJournal of Pain
Volume16
Issue number3
DOIs
StatePublished - Mar 1 2015

Fingerprint

Neuralgia
Simplexvirus
mu Opioid Receptor
Genetic Therapy
Rodentia
Wounds and Injuries
Galanin
Staining and Labeling
Neurons
Spinal Cord
Population
Viruses
Gene Expression
Afferent Neurons
Spinal Ganglia
Cytomegalovirus
Transgenes
Chronic Pain
Up-Regulation
Pain

Keywords

  • Galanin
  • mechanical allodynia
  • mu-opioid receptor
  • nerve injury
  • thermal hyperalgesia

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Neurology
  • Clinical Neurology

Cite this

Injury-specific promoters enhance herpes simplex virus-mediated gene therapy for treating neuropathic pain in rodents. / Smith, Sherika N.; Paige, Candler; Velazquez, Kandy T.; Smith, Terika P.; Raja, Srinivasa Naga; Wilson, Steven P.; Sweitzer, Sarah M.

In: Journal of Pain, Vol. 16, No. 3, 01.03.2015, p. 283-290.

Research output: Contribution to journalArticle

Smith, Sherika N. ; Paige, Candler ; Velazquez, Kandy T. ; Smith, Terika P. ; Raja, Srinivasa Naga ; Wilson, Steven P. ; Sweitzer, Sarah M. / Injury-specific promoters enhance herpes simplex virus-mediated gene therapy for treating neuropathic pain in rodents. In: Journal of Pain. 2015 ; Vol. 16, No. 3. pp. 283-290.
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