Paclitaxel Increases High Voltage-Dependent Calcium Channel Current in Dorsal Root Ganglion Neurons of the Rat

作者：Kawakami Kazuyoshi; Chiba Terumasa; Katagiri Nobuyuki; Saduka Maya; Abe Kenji; Utsunomiya Iku; Hama Toshihiro; Taguchi Kyoji^*

来源：Journal of Pharmacological Sciences, 2012, 120(3): 187-195.

DOI：10.1254/jphs.12123FP

• paclitaxel
• voltage-dependent calcium channel current
• dorsal root ganglion
• gabapentin
• peripheral neuropathy

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 mu M gabapentin. Similar effects in small-diameter DRG neurons were only seen with 100 mu M gabapentin. Western blotting revealed that paclitaxel increased protein levels of the VDCC subunit alpha(2)delta-1 (Ca-v alpha(2)delta-1) in DRG neurons. Immunohistochemistry showed that paclitaxel treatment increased Ca-v alpha(2)delta-1 protein expression in DRG neurons. Thus, paclitaxel treatment increases the VDCC current in small- and medium-diameter DRG neurons and upregulates Ca-v alpha(2)delta-1. The antihyperalgesic action of gabapentin may be due to inhibition of paclitaxel-induced increases in the VDCC current in DRG neurons.

• 出版日期2012-11
• 单位中国医学科学院肿瘤医院