Original Research

Protective Role of Autophagy in Dorsal Root Ganglion to the Mechanical Hyperalgesia Induced By Oxaliplatin in Rats

Yan Kong , Yingqi Weng , Xinran Hou , Qulian Guo
Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China
J Anesth Perioper Med 2018; 5(1): 1- 7 . Published on Jan 31, 2018 . doi:10.24015/JAPM.2018.0012
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Background: Oxaliplatin, a platinum-based chemotherapeutic agent, usually causes an acute peripheral neuropathy. Some research revealed autophagy decreases central sensitization, enhances synaptic plasticity, and relieves the mechanical hyperalgesia in some pathological pain models. 
Methods: We utilized a rat model of acute oxaliplatin induced neuropathy with a single dose of 6 mg/kg and 12 mg/kg oxaliplatin intraperitoneal injection to determine a proper dose. Rats were randomly divided into 3 groups: O+DMSO group, O+Rap group and sham+DMSO group. The rats in three groups were tested mechanical withdrawal threshold the day before oxaliplatin injection and for consecutive 7 days after injection. After finishing behavioral assessment on the 3rd day after injection, some of the rats were sacrificed and the dorsal root ganglion (L4 and L5) were collected for further experiment and measured by Western-blot and immunofluorescence to detect the expression of Beclin 1, LC3-II, and cleaved caspase 3.
Results: The lower dose showed less severe toxicity but also induced significant mechanical hyperalgesia so as being adopted for the following experiment. The autophagy was activated in rats with oxaliplatin injection, and pre-treatment with rapamycin, a strong inducer of autophagy, enhanced the activity of autophagy and ameliorated mechanical hyperalgesia induced by oxaliplatin. This beneficial effect of rapamycin may be attributed to the suppression of apoptosis.
Conclusion: A single administration of oxaliplatin induced autophagy activation with mitochondrial dysfunction, and enhanced autophagy exerted a protective role on mechanical hyperalgesia induced by oxaliplatin. (Funded by the National Natural Science Foundation of China.) 
Citation: Yan Kong, Yingqi Weng, Xinran Hou, Qulian Guo. Protective Role of Autophagy in Dorsal Root Ganglion to the Mechanical Hyperalgesia Induced By Oxaliplatin in Rats. J Anesth Perioper Med 2018;5:1-7. 
doi: 10.24015/JAPM.2018.0012
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