Paclitaxel increases high voltage-dependent calcium channel current in dorsal root ganglion neurons of the rat

Peripheral neuropathic pain is a serious side effect of paclitaxel treatment. however,the mechanism of this paclitaxel-induced neuropathic pain is unknown. in this study,we investigated the effects of paclitaxel on the voltage-dependent calcium channel (vdcc) current in rat dorsal root ganglion (drg) neurons using the whole-cell patch clamp technique. behavioral assessment using von frey filament stimuli showed that 2 and 4 mg/kg paclitaxel treatment induced mechanical allodynia/hyperalgesia. paclitaxel-induced mechanical hyperalgesia was significantly inhibited by gabapentin (100 mg/kg). using the patch clamp method,we observed that paclitaxel (4 mg/kg) treatment significantly increased the vdcc current in small- and medium-diameter drg neurons. moreover,paclitaxel-induced increase in the vdcc current in medium-diameter drg neurons was completely inhibited by 10 and 100 μm gabapentin. similar effects in smalldiameter drg neurons were only seen with 100 μm gabapentin. western blotting revealed that paclitaxel increased protein levels of the vdcc subunit α2δ-1 (cavα 2δ-1) in drg neurons. immunohistochemistry showed that paclitaxel treatment increased cavα2δ-1 protein expression in drg neurons. thus,paclitaxel treatment increases the vdcc current in small- and mediumdiameter drg neurons and upregulates ca vα2δ-1. the antihyperalgesic action of gabapentin may be due to inhibition of paclitaxel-induced increases in the vdcc current in drg neurons. © the japanese pharmacological society.