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

0561141 - ÚŽFG 2023 RIV US eng J - Journal Article
Tadokoro, T. - Bravo-Hernandez, M. - Agashkov, K. - Kobayashi, Y. - Platoshyn, O. - Navarro, M. - Maršala, S. - Miyanohara, A. - Yoshizumi, T. - Shigyo, M. - Krotov, V. - Juhás, Štefan - Juhásová, Jana - Nguyen, The Duong - Kupcová Skalníková, Helena - Motlík, Jan - Studenovská, Hana - Proks, Vladimír - Reddy, R. - Driscoll, S. P. - Glenn, T. D. - Kemthong, T. - Malaivijitnond, S. - Tomori, Z. - Vanický, I. - Kakinohana, M. - Pfaff, S. L. - Ciacci, J. - Belan, P. - Maršala, M.
Precision spinal gene delivery-induced functional switch in nociceptive neurons reverses neuropathic pain.
Molecular Therapy. Roč. 30, č. 8 (2022), s. 2722-2745. ISSN 1525-0016. E-ISSN 1525-0024
R&D Projects: GA MŠMT(CZ) LO1609; GA MŠMT(CZ) EF16_019/0000785; GA MŠMT(CZ) LTAUSA19029
Institutional support: RVO:67985904 ; RVO:61389013
Keywords : neurons * neuropathic pain
OECD category: Neurosciences (including psychophysiology; Neurosciences (including psychophysiology (UMCH-V)
Impact factor: 12.4, year: 2022
Method of publishing: Open access
https://www.sciencedirect.com/science/article/pii/S1525001622002945?via%3Dihub

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.
Permanent Link: https://hdl.handle.net/11104/0333824