Mechanical allodynia and enhanced responses to capsaicin are mediated by PI3K in a paclitaxel model of peripheral neuropathy

Adámek, Pavel; Heleš, Mário; Paleček, Jiří

doi:https://dx.doi.org/10.1016/j.neuropharm.2018.11.027

Number of the records: 1

Mechanical allodynia and enhanced responses to capsaicin are mediated by PI3K in a paclitaxel model of peripheral neuropathy

1.

SYSNO ASEP	0503873
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Mechanical allodynia and enhanced responses to capsaicin are mediated by PI3K in a paclitaxel model of peripheral neuropathy
Author(s)	Adámek, Pavel (FGU-C)_{RID, ORCID, SAI} Heleš, Mário (FGU-C)_{ORCID, RID, SAI} Paleček, Jiří (FGU-C)_{RID, ORCID}
Source Title	Neuropharmacology. - : Elsevier - ISSN 0028-3908 Roč. 146, Mar 1 (2019), s. 163-174
Number of pages	12 s.
Language	eng - English
Country	NL - Netherlands
Keywords	pain ; neuropathy ; chemotherapy ; paclitaxel ; PI3K
Subject RIV	FH - Neurology
OECD category	Neurosciences (including psychophysiology
R&D Projects	GA18-09853S GA ČR - Czech Science Foundation (CSF)
	LQ1604 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
Method of publishing	Limited access
Institutional support	FGU-C - RVO:67985823
UT WOS	000457663900017
EID SCOPUS	85059310372
DOI	10.1016/j.neuropharm.2018.11.027
Annotation	Paclitaxel chemotherapy treatment often leads to neuropathic pain resistant to available analgesic treatments. Recently spinal Toll-like receptor 4 (TLR4) and the transient receptor potential cation channel subfamily V member 1 (TRPV1) were identified to be involved in the pro-nociceptive effect of paclitaxel. The aim of this study was to investigate the role of phosphatidylinositol 3-kinase (PI3K) and serine/threonine kinases in this process, with the use of their antagonists (wortmannin, LY-294002, and staurosporine). The single paclitaxel administration (8 mg/kg i.p.) in mice induced robust mechanical allodynia measured as a reduced threshold to von Frey filament stimulation and generated reduced tachyphylaxis of capsaicin-evoked responses, recorded as changes in mEPSC frequency in patch-clamp recordings of dorsal horn neurons activity in vitro, for up to eight days. Paclitaxel application also induced increased Akt kinase phosphorylation in rat DRG neurons. All these paclitaxel-induced changes were prevented by the wortmannin in vivo pretreatment. Acute co-application of wortmannin or LY-294002 with paclitaxel in spinal cord slices also attenuated the paclitaxel effect on capsaicin-evoked responses. Staurosporine was effective in the acute in vitro experiments and on the first day after the paclitaxel treatment in vivo, but in contrast to wortmannin, it did not have a significant impact later. Our data suggest that the inhibition of PI3K signaling may help alleviate pathological pain syndromes in the paclitaxel-induced neuropathy.
Workplace	Institute of Physiology
Contact	Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400
Year of Publishing	2020
Electronic address	https://doi.org/10.1016/j.neuropharm.2018.11.027

Number of the records: 1