Precision spinal gene delivery-induced functional switch in nociceptive neurons reverses neuropathic pain
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F22%3A00561141" target="_blank" >RIV/61389013:_____/22:00561141 - isvavai.cz</a>
Alternative codes found
RIV/67985904:_____/22:00561141
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S1525001622002945?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S1525001622002945?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ymthe.2022.04.023" target="_blank" >10.1016/j.ymthe.2022.04.023</a>
Alternative languages
Result language
angličtina
Original language name
Precision spinal gene delivery-induced functional switch in nociceptive neurons reverses neuropathic pain
Original language description
Second-order spinal cord excitatory neurons play a key role in spinal processing and transmission of pain signals to the brain. Exogenously induced change in developmentally imprinted excitatory neurotransmitter phenotypes of these neurons to inhibitory has not yet been achieved. Here, we use a subpial dorsal horn-targeted delivery of AAV (adeno-associated virus) vector(s) encoding GABA (gamma-aminobutyric acid) synthe-sizing-releasing inhibitory machinery in mice with neuropathic pain. Treated animals showed a progressive and complete reversal of neuropathic pain (tactile and brush-evoked pain behavior) that persisted for a minimum of 2.5 months post-treatment. The mechanism of this treatment effect results from the switch of excitatory to preferential inhibitory neuro-transmitter phenotype in dorsal horn nociceptive neurons and a resulting increase in inhibitory activity in regional spinal cir-cuitry after peripheral nociceptive stimulation. No detectable side effects (e.g., sedation, motor weakness, loss of normal sensation) were seen between 2 and 13 months post-treatment in naive adult mice, pigs, and non-human primates. The use of this treatment approach may represent a potent and safe treat-ment modality in patients suffering from spinal cord or periph-eral nerve injury-induced neuropathic pain.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30103 - Neurosciences (including psychophysiology)
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Molecular Therapy
ISSN
1525-0016
e-ISSN
1525-0024
Volume of the periodical
30
Issue of the periodical within the volume
8
Country of publishing house
US - UNITED STATES
Number of pages
24
Pages from-to
2722-2745
UT code for WoS article
000842995100009
EID of the result in the Scopus database
2-s2.0-85130358802