HSV vector-mediated GAD67 suppresses neuropathic pain induced by perineural HIV gp120 in rats through inhibition of ROS and Wnt5a

HSV vector-mediated GAD67 suppresses neuropathic pain induced by perineural HIV gp120 in rats through inhibition of ROS and Wnt5a

Human immunodeficiency virus (HIV)-related neuropathic pain is a debilitating chronic condition that is severe and unrelenting. Despite the extensive research, the exact neuropathological mechanisms remain unknown, which hinders our ability to develop effective treatments. Loss of GABAergic tone may...

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Main Authors: Kanda, Hirotsugu, Kanao, Megumi, Liu, Shue, Yi, Hyun, Iida, Takafumi, Levitt, Roy C, Candiotti, Keith A, Lubarsky, David A, Hao, Shuanglin
Format: Online
Language:English
Published: 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4824655/
id pubmed-4824655
recordtype oai_dc
spelling pubmed-48246552016-07-11 HSV vector-mediated GAD67 suppresses neuropathic pain induced by perineural HIV gp120 in rats through inhibition of ROS and Wnt5a Kanda, Hirotsugu Kanao, Megumi Liu, Shue Yi, Hyun Iida, Takafumi Levitt, Roy C Candiotti, Keith A Lubarsky, David A Hao, Shuanglin Article Human immunodeficiency virus (HIV)-related neuropathic pain is a debilitating chronic condition that is severe and unrelenting. Despite the extensive research, the exact neuropathological mechanisms remain unknown, which hinders our ability to develop effective treatments. Loss of GABAergic tone may play an important role in the neuropathic pain state. Glutamic acid decarboxylase 67 (GAD67) is one of isoforms that catalyze GABA synthesis. Here, we used recombinant herpes simplex virus (HSV-1) vectors that encode gad1 gene to evaluate the therapeutic potential of GAD67 in peripheral HIV gp120-induced neuropathic pain in rats. We found that 1) subcutaneous inoculation of the HSV vectors expressing GAD67 attenuated mechanical allodynia in the model of HIV gp120-induced neuropathic pain, 2) the anti-allodynic effect of GAD67 was reduced by GABA-A and-B receptors antagonists, 3) HSV vectors expressing GAD67 reversed the lowered GABA-IR expression, and 4) the HSV vectors expressing GAD67 suppressed the upregulated mitochondrial superoxide and Wnt5a in the spinal dorsal horn. Taken together, our studies support the concept that recovering GABAergic tone by the HSV vectors may reverse HIV-associated neuropathic pain through suppressing mitochondrial superoxide and Wnt5a. Our studies provide validation of HSV-mediated GAD67 gene therapy in the treatment of HIV-related neuropathic pain. 2016-01-11 2016-04 /pmc/articles/PMC4824655/ /pubmed/26752351 http://dx.doi.org/10.1038/gt.2016.3 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Kanda, Hirotsugu
Kanao, Megumi
Liu, Shue
Yi, Hyun
Iida, Takafumi
Levitt, Roy C
Candiotti, Keith A
Lubarsky, David A
Hao, Shuanglin
spellingShingle Kanda, Hirotsugu
Kanao, Megumi
Liu, Shue
Yi, Hyun
Iida, Takafumi
Levitt, Roy C
Candiotti, Keith A
Lubarsky, David A
Hao, Shuanglin
HSV vector-mediated GAD67 suppresses neuropathic pain induced by perineural HIV gp120 in rats through inhibition of ROS and Wnt5a
author_facet Kanda, Hirotsugu
Kanao, Megumi
Liu, Shue
Yi, Hyun
Iida, Takafumi
Levitt, Roy C
Candiotti, Keith A
Lubarsky, David A
Hao, Shuanglin
author_sort Kanda, Hirotsugu
title HSV vector-mediated GAD67 suppresses neuropathic pain induced by perineural HIV gp120 in rats through inhibition of ROS and Wnt5a
title_short HSV vector-mediated GAD67 suppresses neuropathic pain induced by perineural HIV gp120 in rats through inhibition of ROS and Wnt5a
title_full HSV vector-mediated GAD67 suppresses neuropathic pain induced by perineural HIV gp120 in rats through inhibition of ROS and Wnt5a
title_fullStr HSV vector-mediated GAD67 suppresses neuropathic pain induced by perineural HIV gp120 in rats through inhibition of ROS and Wnt5a
title_full_unstemmed HSV vector-mediated GAD67 suppresses neuropathic pain induced by perineural HIV gp120 in rats through inhibition of ROS and Wnt5a
title_sort hsv vector-mediated gad67 suppresses neuropathic pain induced by perineural hiv gp120 in rats through inhibition of ros and wnt5a
description Human immunodeficiency virus (HIV)-related neuropathic pain is a debilitating chronic condition that is severe and unrelenting. Despite the extensive research, the exact neuropathological mechanisms remain unknown, which hinders our ability to develop effective treatments. Loss of GABAergic tone may play an important role in the neuropathic pain state. Glutamic acid decarboxylase 67 (GAD67) is one of isoforms that catalyze GABA synthesis. Here, we used recombinant herpes simplex virus (HSV-1) vectors that encode gad1 gene to evaluate the therapeutic potential of GAD67 in peripheral HIV gp120-induced neuropathic pain in rats. We found that 1) subcutaneous inoculation of the HSV vectors expressing GAD67 attenuated mechanical allodynia in the model of HIV gp120-induced neuropathic pain, 2) the anti-allodynic effect of GAD67 was reduced by GABA-A and-B receptors antagonists, 3) HSV vectors expressing GAD67 reversed the lowered GABA-IR expression, and 4) the HSV vectors expressing GAD67 suppressed the upregulated mitochondrial superoxide and Wnt5a in the spinal dorsal horn. Taken together, our studies support the concept that recovering GABAergic tone by the HSV vectors may reverse HIV-associated neuropathic pain through suppressing mitochondrial superoxide and Wnt5a. Our studies provide validation of HSV-mediated GAD67 gene therapy in the treatment of HIV-related neuropathic pain.
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4824655/
_version_ 1613563793563975680

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