The Role Of Glial Cells In Chemotherapy-induced Neuropathic Pain

Object To set up an animal model of chemotherapy-induced neuropathic pain. By observing the activation of glial cells, we study the mechanism of chemotherapy-induced neuropathic pain. Further, we explore the therapy of chemotherapy-induced neuropathic pain preliminary.Methods We adapted a model by using repeated intraperitoned injection of vincristine and paclitaxel respectively. By immunohistochemical technique, the expression of specific activation markers of astrocytes and microglials, glial fibrillary acidic protein (GFAP) and OX-42 respectively, were examined in brain , lumbar intumescentia and hippocampi. And deploying RT-PCR techniques, the mRNA of interleukine-1β(IL-1β) and glial cell line-derived neurotrophic factor (GDNF) were tested. The change of protein P38 in microglial cells was evaluated by Western-blotting analysis. By the use of electron microscope, we observed the morphological change in the dorsal horn of spine. Paclitaxel induced neuropathic pain was attend to be cured by concurrently injection of thymosin alpha 1. The expression of GDNF affected by paclitaxel with or without treatment of thymosin, was analyzed.Results In vincristine group, mechanical hyperalgsia appeared on the 8th day and thermal hyperalgsia on the 5th day of vincristine injection. Tactile paw withdrawal threshold decreased to minimum on the 12th day of treatment. Glial cells were obviously activated in periaquenductal gray and lumbar spinal gray in chemotherapy group. IL-1βexpression increased in vincristine group, while GDNF was decreased. After primary injection of paclitaxel, mechanical hyperalgsia appeared on the 16th day, while thermal hyperalgsia was not observed. Both astrosytes and microglial cells widely activated in brain , lumbar intumescentia and hippocampi and the protein P38 was augmented in lumbar spine. The demyelination of nerve fibres instead of ultramicro-morphological activation of glial cells was observed. The injection of thymosin alpha 1 produced 30.8% reversal of mechanical hyperalgesia meanwhile GDNF was up-regulate by thymosin alpha 1.Conclusion The animal modal we adept accorded with the basic character of neuropathic pain. Glial cells were actived in vincristine and paclitaxel-induced neuropathic pain. The change of expression of IL-1βand GDNF were involved in neuropathic pain evoked by vincristine and paclitaxel. P38 contributes to the mediation of glial cells activated by chemotherapy. Thymosin alpha 1 can be partly reversed paclitaxel induced neuropathic pain. Thymosin alpha 1 can spur the expression of GDNF, maybe by which it relieved paclitaxel induced neuropathic pain.