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

T. Tadokoro, M. Bravo-Hernandez, K. Agashkov, Y. Kobayashi, O. Platoshyn, M. Navarro, S. Marsala, A. Miyanohara, T. Yoshizumi, M. Shigyo, V. Krotov, S. Juhas, J. Juhasova, D. Nguyen, H. Kupcova Skalnikova, J. Motlik, H. Studenovska, V. Proks, R....

. 2022 ; 30 (8) : 2722-2745. [pub] 20220505

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, práce podpořená grantem, Research Support, N.I.H., Extramural

Perzistentní odkaz   https://www.medvik.cz/link/bmc22024925

Grantová podpora
R01 NS113189 NINDS NIH HHS - United States

E-zdroje Online Plný text

NLK Free Medical Journals od 2000 do Před 1 rokem
Freely Accessible Science Journals od 2000 do Před 1 rokem
PubMed Central od 2009 do Před 1 rokem
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Open Access Digital Library od 2000-01-01
Elsevier Open Access Journals od 2000-01-01 do 2023-06-07
Elsevier Open Archive Journals od 2000-01-01 do Před 1 rokem

Odkazy

PubMed 35524407
DOI 10.1016/j.ymthe.2022.04.023
Knihovny.cz E-zdroje

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) synthesizing-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 neurotransmitter phenotype in dorsal horn nociceptive neurons and a resulting increase in inhibitory activity in regional spinal circuitry 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 treatment modality in patients suffering from spinal cord or peripheral nerve injury-induced neuropathic pain.

Citace poskytuje Crossref.org

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