Adenovector GAD65 gene delivery into the rat trigeminal ganglion produces orofacial analgesia.
BACKGROUND
Our goal is to use gene therapy to alleviate pain by targeting glial cells. In an animal model of facial pain we tested the effect of transfecting the glutamic acid decarboxylase (GAD) gene into satellite glial cells (SGCs) of the trigeminal ganglion by using a serotype 5 adenovector with high tropisms for glial cells. We postulated that GABA produced from the expression of GAD would reduce pain behavior by acting on GABA receptors on neurons within the ganglion.


RESULTS
Injection of adenoviral vectors (AdGAD65) directly into the trigeminal ganglion leads to sustained expression of the GAD65 isoform over the 4 weeks observation period. Immunohistochemical analysis showed that adenovirus-mediated GAD65 expression and GABA synthesis were mainly in SGCs. GABAA and GABAB receptors were both seen in sensory neurons, yet only GABAA receptors decorated the neuronal surface. GABA receptors were not found on SGCs. Six days after injection of AdGAD65 into the trigeminal ganglion, there was a statistically significant decrease of pain behavior in the orofacial formalin test, a model of inflammatory pain. Rats injected with control virus (AdGFP or AdLacZ) had no reduction in their pain behavior. AdGAD65-dependent analgesia was blocked by bicuculline, a selective GABAA receptor antagonist, but not by CGP46381, a selective GABAB receptor antagonist.


CONCLUSIONS
Transfection of glial cells in the trigeminal ganglion with the GAD gene blocks pain behavior by acting on GABAA receptors on neuronal perikarya.
Vit
Jean-Philippe
JP
Department of Anatomy, University of California San Francisco, San Francisco, CA 94143, USA. Jeanpvit@gmail.com
Ohara
Peter T
PT
Sundberg
Christopher
C
Rubi
Blanca
B
Maechler
Pierre
P
Liu
Chunyan
C
Puntel
Mariana
M
Lowenstein
Pedro
P
Castro
Maria
M
Jasmin
Luc
L
D000256:Adenoviridae / Q000235:genetics*; D000698:Analgesia / Q000379:methods; D000818:Animals; D002645:Chickens; D005157:Facial Pain / Q000628:therapy*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012668:Trigeminal Ganglion / Q000378:metabolism*
D005968:Glutamate Decarboxylase