Adenovector GAD65 gene delivery into the rat trigeminal ganglion produces orofacial analgesia

VIT; OHARA; SUNDBERG; RUBI; MAECHLER; LIU; PUNTEL; LOWENSTEIN; CASTRO; JASMIN

MOLECULAR PAIN

BioMed Central Ltd.

Año: 2009

1744-8069

Background: Our goal is to use gene therapy to alleviate pain by targeting glial cells. In an animalmodel of facial pain we tested the effect of transfecting the glutamic acid decarboxylase (GAD) geneinto satellite glial cells (SGCs) of the trigeminal ganglion by using a serotype 5 adenovector withhigh tropisms for glial cells. We postulated that GABA produced from the expression of GADwould 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 tosustained expression of the GAD65 isoform over the 4 weeks observation period.Immunohistochemical analysis showed that adenovirus-mediated GAD65 expression and GABAsynthesis 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 onSGCs. Six days after injection of AdGAD65 into the trigeminal ganglion, there was a statisticallysignificant 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.Conclusion: Transfection of glial cells in the trigeminal ganglion with the GAD gene blocks painbehavior by acting on GABAA receptors on neuronal perikarya.