Vector-mediated release of GABA attenuates pain-related behaviors and reduces Na(V)1.7 in DRG neurons

Munmun Chattopadhyay, Marina Mata, David J Fink
European Journal of Pain: EJP 2011, 15 (9): 913-20
Pain is a common and debilitating accompaniment of neuropathy that occurs as a complication of diabetes. In the current study, we examined the effect of continuous release of gamma amino butyric acid (GABA), achieved by gene transfer of glutamic acid decarboxylase (GAD67) to dorsal root ganglia (DRG) in vivo using a non-replicating herpes simplex virus (HSV)-based vector (vG) in a rat model of painful diabetic neuropathy (PDN). Subcutaneous inoculation of vG reduced mechanical hyperalgesia, thermal hyperalgesia and cold allodynia in rats with PDN. Continuous release of GABA from vector transduced cells in vivo prevented the increase in the voltage-gated sodium channel isoform 1.7 (Na(V)1.7) protein that is characteristic of PDN. In vitro, infection of primary DRG neurons with vG prevented the increase in Na(V)1.7 resulting from exposure to hyperglycemia. The effect of vector-mediated GABA on Na(V)1.7 levels in vitro was blocked by phaclofen but not by bicuculline, a GABA(B) receptor effect that was blocked by pertussis toxin-(PTX) interference with Gα((i/o)) function. Taken in conjunction with our previous observation that continuous activation of delta opioid receptors by vector-mediated release of enkephalin also prevents the increase in Na(V)1.7 in DRG exposed to hyperglycemia in vitro or in vivo, the observations in this report suggest a novel common mechanism through which activation of G protein coupled receptors (GPCR) in DRG neurons regulate the phenotype of the primary afferent.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"