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  • Title: Paclitaxel increases high voltage-dependent calcium channel current in dorsal root ganglion neurons of the rat.
    Author: Kawakami K, Chiba T, Katagiri N, Saduka M, Abe K, Utsunomiya I, Hama T, Taguchi K.
    Journal: J Pharmacol Sci; 2012; 120(3):187-95. PubMed ID: 23090716.
    Abstract:
    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 (Ca(v)α₂δ-1) in DRG neurons. Immunohistochemistry showed that paclitaxel treatment increased Ca(v)α₂δ-1 protein expression in DRG neurons. Thus, paclitaxel treatment increases the VDCC current in small- and medium-diameter DRG neurons and upregulates Ca(v)α₂δ-1. The antihyperalgesic action of gabapentin may be due to inhibition of paclitaxel-induced increases in the VDCC current in DRG neurons.
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