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CX3CR1-Mediated Akt1 Activation Contributes to the Paclitaxel-Induced Painful Peripheral Neuropathy in Rats

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Abstract

Painful peripheral neuropathy is a serious dose-limiting side effect of paclitaxel therapy, which unfortunately often happens during the optimal clinical management of chemotherapy in cancer patients. Currently the underlying mechanisms of the painful peripheral neuropathy remain largely unknown. Here, we found that paclitaxel treatment (3 × 8 mg/kg, cumulative dose 24 mg/kg) upregulated the expression of CX3CR1 and phosphorylated Akt1 in DRG and spinal dorsal horn. Blocking of Akt1 pathway activation with different inhibitor (MK-2206 or LY294002) significantly attenuated mechanical allodynia and thermal hyperalgesia induced by paclitaxel. Furthermore, inhibition of CX3CR1 by using neutralizing antibody not only prevented Akt1 activation in DRG and spinal dorsal horn but also alleviated pain-related behavior induced by paclitaxel treatment. This study suggested that CX3CR1/Akt1 signaling pathway may be a potential target for prevention and reversion of the painful peripheral neuropathy induced by paclitaxel.

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Acknowledgements

This study was funded by National Natural Science Foundation of China (81070894), 1255 Discipline Construction Program Foundation of the First Affiliated Hospital of SMMU(125532200), and Guangdong provincial science and technology project (2013B022000029), People’s Republic of China.

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    Authors and Affiliations

    1. Department of Anesthesiology and Critical Care, The First Affiliated Hospital, Second Military Medical University, 168 Changhai Road, Shanghai, 200433, People’s Republic of China

      Dai Li, Hui Chen & Yuan-Chang Xiong

    2. Center For Reproductive Medicine, Guangzhou First People’s Hospital, Guangzhou Medical University, No.1 Panfu Road, Guangzhou, 510180, People’s Republic of China

      Xiao-Huan Luo & Wei Xia

    3. Department of Pain, Branch of The First Affiliate Hospital of Xinjiang Medical University, Changji, People’s Republic of China

      Yang Sun

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    1. Dai Li
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    2. Hui Chen
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    3. Xiao-Huan Luo
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    Correspondence to Wei Xia or Yuan-Chang Xiong.

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    Dai Li and Hui Chen have contributed equally to this work.

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    Li, D., Chen, H., Luo, XH. et al. CX3CR1-Mediated Akt1 Activation Contributes to the Paclitaxel-Induced Painful Peripheral Neuropathy in Rats. Neurochem Res 41, 1305–1314 (2016). https://doi.org/10.1007/s11064-016-1827-y

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