Mechanical allodynia and enhanced responses to capsaicin are mediated by PI3K in a paclitaxel model of peripheral neuropathy
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
30471295
DOI
10.1016/j.neuropharm.2018.11.027
PII: S0028-3908(18)30446-5
Knihovny.cz E-resources
- MeSH
- Posterior Horn Cells drug effects metabolism MeSH
- Excitatory Postsynaptic Potentials drug effects MeSH
- Phosphatidylinositol 3-Kinases metabolism MeSH
- Hyperalgesia chemically induced drug therapy metabolism MeSH
- Protein Kinase Inhibitors pharmacology MeSH
- Capsaicin pharmacology MeSH
- Transient Receptor Potential Channels MeSH
- TRPV Cation Channels metabolism MeSH
- Rats MeSH
- Lipopolysaccharides pharmacology MeSH
- Spinal Cord drug effects metabolism MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Neuralgia chemically induced drug therapy metabolism MeSH
- Oncogene Protein v-akt metabolism MeSH
- Paclitaxel toxicity MeSH
- Peptide Fragments immunology metabolism MeSH
- Rats, Wistar MeSH
- Protein Serine-Threonine Kinases antagonists & inhibitors metabolism MeSH
- Protein Kinase C immunology metabolism MeSH
- Signal Transduction drug effects MeSH
- Toll-Like Receptor 4 metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Protein Kinase Inhibitors MeSH
- Capsaicin MeSH
- Transient Receptor Potential Channels MeSH
- TRPV Cation Channels MeSH
- lipopolysaccharide A MeSH Browser
- Lipopolysaccharides MeSH
- Oncogene Protein v-akt MeSH
- Paclitaxel MeSH
- Peptide Fragments MeSH
- protein kinase C (19-31) MeSH Browser
- Protein Serine-Threonine Kinases MeSH
- Protein Kinase C MeSH
- Toll-Like Receptor 4 MeSH
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.
References provided by Crossref.org
Anandamide-Mediated Modulation of Nociceptive Transmission at the Spinal Cord Level
