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

Journal of Pharmacological Sciences

Iku Utsunomiya⁴  Terumasa Chiba¹  Nobuyuki Katagiri⁴  Kazuyoshi Kawakami¹  Kenji Abe²  Kyoji Taguchi¹  Maya Saduka¹  Toshihiro Hama³ 

[1] Department of Medicinal Pharmacology, Showa Pharmaceutical University, Japan;Department of Pharmacology, School of Pharmaceutical Sciences, Ohu University, Japan;Department of Pharmacy, Cancer Institute Hospital, Japan;Department of Pharmacotherapeutics, Showa Pharmaceutical University, Japan

关键词: paclitaxel;    voltage-dependent calcium channel current;    dorsal root ganglion;    gabapentin;    peripheral neuropathy;   

DOI  :  10.1254/jphs.12123FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(36)Cited-By(12)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 small-diameter DRG neurons were only seen with 100 μM gabapentin. Western blotting revealed that paclitaxel increased protein levels of the VDCC subunit α2δ-1 (Cavα2δ-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 medium-diameter DRG neurons and upregulates Cavα2δ-1. The antihyperalgesic action of gabapentin may be due to inhibition of paclitaxel-induced increases in the VDCC current in DRG neurons.

【 授权许可】

Unknown