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

Mechanical allodynia and enhanced responses to capsaicin are mediated by PI3K in a paclitaxel model of peripheral neuropathy. Neuropharmacology. 2018 Nov 21;: Authors: Adamek P, Heles M, Palecek J Abstract 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 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 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...
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Neuropharmacology Source Type: research