Effects of transgene-mediated endomorphin-2 in inflammatory pain
by
Hao S, Wolfe D, Glorioso JC, Mata M, Fink DJ.
Department of Neurology and VA Ann Arbor Healthcare System,
Ann Arbor, MI, USA.
Eur J Pain. 2009 Apr;13(4):380-6.


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 mu 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.
Pain
Analogs
Interactions
Knockout mice
Endomorphins 1 and 2
Endomorphins and the mouse
The rewards of endomorphin 1
Endomorphins and rodent brains
Adenylyl cyclase superactivation
The degradation of endomorphins
Endomorphinergic neurons in the CNS
Endomorphins and the mu-opioid receptor
Endomorphins and related opioid peptides
Endomorphins 1 and 2 as antidepressants
Morphine: a mood-brightening smart-drug?
Opioids, depression and learned helplessness
Rewarding and psychomotor stimulant effects of endomorphin 1
Endomorphin-1, accumbal dopamine and the mu-opioid receptor
How to increase blood-brain barrier penetration of endomorphin 1
Biosynthesis of the mu-opioid receptor agonists endomorphins 1 and 2


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