Constitutive GABA expression via a recombinant adeno-associated virus consistently attenuates neuropathic pain.
Peripheral neuropathic pain is a common clinical problem with few existing treatments. Previously, we constructed rAAV bearing GAD65 and demonstrated that GAD65 and GABA can be constitutively produced in the CNS. To investigate the beneficial effects of GAD65 produced by rAAV and resulting GABA release in peripheral neuropathic pain, we established a neuropathic pain rat model. The direct administration of rAAV-GAD65 to dorsal root ganglion induced constitutive GAD65 expression, which was readily detected by immunohistochemistry. Both allodynic and hyperalgeic behavior tests suggested that neuropathic pain was noticeably reduced, along with the transgenic GAD65 expression. Moreover, the magnitude of pain relief was maintained during the entire experimental period. Concomitantly, the significant enhancement in GABA release following transgenic GAD65 expression was identified in vivo. Taken all together, these results provide evidence that persistent GAD65 and subsequent GABA expression in DRGs via rAAV effectively attenuates peripheral neuropathic pain for long period of time.
Lee
Boyoung
B
Department of Neurosurgery, Yonsei University College of Medicine, CPO Box 8044, Seoul, Republic of Korea.
Kim
Jaehyung
J
Kim
Sung Jin
SJ
Lee
Heuiran
H
Chang
Jin Woo
JW
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D015316:Genetic Therapy / Q000379:methods*; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D009437:Neuralgia / Q000503:physiopathology* / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism / Q000627:therapeutic use; D014162:Transfection / Q000379:methods*; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*
D007527:Isoenzymes; D011994:Recombinant Proteins; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2