The Characteristics Of Neuropathic Pain Induced By Docetaxel In Rats

PartⅠComparison of Neuropathic pain Induced by Paclitaxel and Docetaxel in RatsObjective:To compare the different characteristics of paclitaxel and docetaxel induced neuropathic pain in rats.Methods:Thirty-two male SD rats were randomly divided into four groups:naive control, vehicle control, paclitaxel group and docetaxel group. Mechanical threshold, heat threshold, cold allodynia were examined on day8and two rats from each group were sacrificed to obtain the sciatic nerve for neuropathological examination.Results:paclitaxel arouse mechanical allodynia, mechanical hyperalgesia and cold allodynia, without heat threshold. Meanwhile, docetaxel induced mechanical allodynia, mechanical hyperalgesia, heat hypoalgesia, and cold allodynia. Both of them impaired the sciatic nerve, but paclitaxel showed more myelinated fiber damage than docetaxel.Conclusion:Though taxanes (paclitaxel and docetaxel) are widely used in clinical, they have the different characteristics of neuropathic pain. Part ⅡBehavioral and Neuropathological Studies in Rats with a Single Docetaxel InjectionObjective:To determine the characteristics of neuropathic pain induced by a single intravenous injection of docetaxel in a rat model.Methods:A total of36SD rats were divided into four groups, vehicle control and three different doses of single docetaxel injection. Eight days after injection, behavioral testing, analysis of the expression of substance P in the lumbar spinal cord using immunohistochemistry, and a morphological analysis of the sciatic nerve by electron microscopy were performed.Results:We found that a single injection of docetaxel in rats can produce mechanical allodynia and heat hyperalgesia without changes in Rota-Rod results. The levels of substance P in the spine were increased after docetaxel injection. Electron microscopy revealed severed unmyelinated fiber impairment associated with mild myelinated degeneration in the sciatic nerve eight days after docetaxel injection.Conclusion:These results demonstrate that this new rat model can reproduce the characteristics of peripheral neuropathy observed in clinical practice, making it a useful tool for the investigation of the mechanisms underlying docetaxel-induced neuropathy and for the prescreening of neuroprotective agents. PartⅢEffect of Pregabalin on Docetaxel-induced Neuropathic pain in RatsObjective:To investigate the potential efficacy of pregabalin in docetaxel-induced neuropathic pain in rats. Methods:A total of35male SD rats were randomly divided into5groups:naive control, pregabalin administrated (30mg/kg p.o.) for8days, a single docetaxel injection (10mg/kg i.v.), and pregabalin followed by docetaxel for8days (10mg/kg and30mg/kg p.o.). On day8, mechanical threshold, heat threshold, cold allodynia, substance P and CGRP release in L4-6DRG in the lumbar spinal cord by RT-PCR were examined.Results:Docetaxel can evoke mechanical allodynia, heat hypoalgesia, cold allodynia, substance P and CGRP release in L4-6DRG. However, oral administration of pregabalin (10mg/kg and30mg/kg) for8consecutive days significantly ameliorated docetaxel-induced neuropathic pain by alleviating heat hypoalgesia, cold allodynia, and reducing the substance P and CGRP release, without changing mechanical allodynia.Conclusion:Pregabalin may be a potential treatment agent against chemotherapy-induced neuropathic pain.