Precision spinal gene delivery-induced functional switch in nociceptive neurons reverses neuropathic pain

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/67985904:_____/22:00561141

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Precision spinal gene delivery-induced functional switch in nociceptive neurons reverses neuropathic pain

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Precision spinal gene delivery-induced functional switch in nociceptive neurons reverses neuropathic pain

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Molecular Therapy

ISSN

1525-0016

e-ISSN

1525-0024

Svazek periodika

30

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

24

Strana od-do

2722-2745

Kód UT WoS článku

000842995100009

EID výsledku v databázi Scopus

2-s2.0-85130358802