Počet záznamů: 1
Dual PI3Kδ/γ Inhibitor Duvelisib Prevents Development of Neuropathic Pain in Model of Paclitaxel-Induced Peripheral Neuropathy
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SYSNO ASEP 0556128 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Dual PI3Kδ/γ Inhibitor Duvelisib Prevents Development of Neuropathic Pain in Model of Paclitaxel-Induced Peripheral Neuropathy Tvůrce(i) Adámek, Pavel (FGU-C) RID, ORCID, SAI
Heleš, Mário (FGU-C) ORCID, RID, SAI
Bhattacharyya, Anirban (FGU-C) RID, SAI, ORCID
Pontearso, Monica (FGU-C) ORCID
Slepička, Jakub (FGU-C) ORCID
Paleček, Jiří (FGU-C) RID, ORCIDZdroj.dok. Journal of Neuroscience. - : Society for Neuroscience - ISSN 0270-6474
Roč. 42, č. 9 (2022), s. 1864-1881Poč.str. 18 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova spinal-cord ; dorsal horn ; glycine ; neuropathy ; pain ; pi3k ; trpv1 Obor OECD Neurosciences (including psychophysiology CEP GA20-19136S GA ČR - Grantová agentura ČR Způsob publikování Open access Institucionální podpora FGU-C - RVO:67985823 UT WOS 000766775600005 EID SCOPUS 85125680816 DOI 10.1523/JNEUROSCI.1324-21.2021 Anotace The development of painful paclitaxel-induced peripheral neuropathy (PIPN) represents a major dose-limiting side effect of paclitaxel chemotherapy. Here we report a promising effect of duvelisib (Copiktra), a novel FDA-approved PI3Kδ/γ isoform-specific inhibitor, in preventing paclitaxel-induced pain-like behavior and pronociceptive signaling in DRGs and spinal cord dorsal horn (SCDH) in rat and mouse model of PIPN. Duvelisib blocked the development of mechanical hyperalgesia in both males and females. Moreover, duvelisib prevented paclitaxel-induced sensitization of TRPV1 receptors, and increased PI3K/Akt signaling in small-diameter DRG neurons and an increase of CD68+ cells within DRGs. Specific optogenetic stimulation of inhibitory neurons combined with patch-clamp recording revealed that duvelisib inhibited paclitaxel-induced weakening of inhibitory, mainly glycinergic control on SCDH excitatory neurons. Enhanced excitatory and reduced inhibitory neurotransmission in the SCDH following PIPN was also alleviated by duvelisib application. In summary, duvelisib showed a promising ability to prevent neuropathic pain in PIPN. The potential use of our findings in human medicine may be augmented by the fact that duvelisib is an FDA-approved drug with known side effects. Pracoviště Fyziologický ústav Kontakt Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Rok sběru 2023 Elektronická adresa https://doi.org/10.1523/JNEUROSCI.1324-21.2021
Počet záznamů: 1