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.

• 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