Effects of transgene-mediated endomorphin-2 in inflammatory pain

Shuanglin Hao, Darren Wolfe, Joseph C. Glorioso, Marina Mata, David J. Fink

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

We examined the analgesic properties of endomorphin-2 expressed in DRG neurons transduced with a non-replicating herpes simplex virus (HSV)-based vector containing a synthetic endomorphin-2 gene construct. HSV-mediated endomorphin-2 expression reduced nocisponsive behaviors in response to mechanical and thermal stimuli after injection of complete Freund's adjuvant (CFA) into the paw, and reduced peripheral inflammation measured by paw swelling after injection of CFA. The analgesic effect of the vector was blocked by either intraperitoneal or intrathecal administration of naloxone methiodide, blocking peripheral and central μ opioid receptors, respectively. Endomorphin-2 vector injection also reduced spontaneous pain-related behaviors in the delayed phase of the formalin test and in both CFA and formalin models suppressed spinal c-fos expression. The magnitude of the vector-mediated analgesic effect on the delayed phase of the formalin test was similar in naïve animals and in animals with opiate tolerance induced by twice daily treatment with morphine, suggesting that there was no cross-tolerance between vector-mediated endomorphin-2 and morphine. These results suggest that transgene-mediated expression of endomorphin-2 in transduced DRG neurons in vivo acts both peripherally and centrally through mu opioid receptors to reduce pain perception.

Original languageEnglish (US)
Pages (from-to)380-386
Number of pages7
JournalEuropean Journal of Pain
Volume13
Issue number4
DOIs
StatePublished - Apr 2009
Externally publishedYes

Keywords

  • Endomorphin-2
  • Gene therapy
  • Herpes simplex virus
  • Inflammatory pain
  • Opiates

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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