Transgene-mediated enkephalin release enhances the effect of morphine and evades tolerance to produce a sustained antiallodynic effect in neuropathic pain

Shuanglin Hao, Marina Mata, William Goins, Joseph C. Glorioso, David J. Fink

Research output: Contribution to journalArticle

114 Scopus citations

Abstract

We examined the pharmacologic characteristics of herpes simplex virus (HSV) vector-mediated expression of proenkephalin in the dorsal root ganglion in a rodent model of neuropathic pain. We found that: (i) vector-mediated enkephalin produced an antiallodynic effect that was reversed by naloxone; (ii) vector-mediated enkephalin production in animals with spinal nerve ligation prevented the induction of c-fos expression in second order sensory neurons in the dorsal horn of spinal cord; (iii) the effect of vector-mediated enkephalin enhanced the effect of morphine, reducing the ED50 of morphine 10-fold; (iv) animals did not develop tolerance to the continued production of vector-mediated enkephalin over a period of several weeks; and, (v) vector transduction continued to provide an analgesic effect despite the induction of tolerance to morphine. This is the first demonstration of gene transfer to provide an analgesic effect in neuropathic pain. The pharmacologic analysis demonstrates that transgene-mediated expression and local release of opioid peptides produce some effects that are distinct from peptide analogues delivered pharmacologically.

Original languageEnglish (US)
Pages (from-to)135-142
Number of pages8
JournalPain
Volume102
Issue number1-2
DOIs
StatePublished - Mar 2003
Externally publishedYes

Keywords

  • Gene transfer
  • Herpes simplex virus
  • Morphine
  • Pain
  • Tolerance

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Neurology
  • Neuroscience(all)
  • Pharmacology
  • Clinical Psychology

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