title: CX3CR1-Mediated Akt1 Activation Contributes to the Paclitaxel-Induced Painful Peripheral Neuropathy in Rats.
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.
authors.affiliation: Department of Anesthesiology and Critical Care, The First Affiliated Hospital, Second Military Medical University, 168 Changhai Road, Shanghai, 200433, People's Republic of China.
authors.forename: Dai
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Anesthesiology and Critical Care, The First Affiliated Hospital, Second Military Medical University, 168 Changhai Road, Shanghai, 200433, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Center For Reproductive Medicine, Guangzhou First People's Hospital, Guangzhou Medical University, No.1 Panfu Road, Guangzhou, 510180, People's Republic of China.
authors.forename: Xiao-Huan
authors.initials: XH
authors.lastname: Luo
authors.affiliation: Department of Pain, Branch of The First Affiliate Hospital of Xinjiang Medical University, Changji, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Center For Reproductive Medicine, Guangzhou First People's Hospital, Guangzhou Medical University, No.1 Panfu Road, Guangzhou, 510180, People's Republic of China. rose-xw@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Xia
authors.affiliation: Department of Anesthesiology and Critical Care, The First Affiliated Hospital, Second Military Medical University, 168 Changhai Road, Shanghai, 200433, People's Republic of China. proychxiong@163.com.
authors.forename: Yuan-Chang
authors.initials: YC
authors.lastname: Xiong
mesh_terms: D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D008297:Male; D017239:Paclitaxel / Q000633:toxicity*; D010146:Pain / Q000139:chemically induced / Q000378:metabolism*; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019707:Receptors, Chemokine / Q000096:biosynthesis*
chemical_list: D000073883:CX3C Chemokine Receptor 1; C516305:CX3CR1 protein, rat; D019707:Receptors, Chemokine; C494920:Akt1 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D017239:Paclitaxel
keywords: Akt; CX3CR1; Paclitaxel; Peripheral neuropathy