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Effects of transgene‐mediated endomorphin‐2 in inflammatory pain
Author(s) -
Hao Shuanglin,
Wolfe Darren,
Glorioso Joseph C.,
Mata Marina,
Fink David J.
Publication year - 2009
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1016/j.ejpain.2008.05.008
Subject(s) - transgene , medicine , pharmacology , biology , genetics , gene
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.