Nrf2 activation ameliorates mechanical allodynia in paclitaxel-induced neuropathic pain  

作　　者：Ya-qun Zhou Dai-qiang Liu Shu-ping Chen Nan Chen Jia Sun Xiao-mei Wang Fei Cao Yu-ke Tian Da-wei Ye 

机构地区：[1]Department of Anesthesiology and Pain Medicine,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China [2]Department of Psychiatry,UMKC School of Medicine,Kansas City,MO 64108,USA [3]Cancer Center,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China

出　　处：《Acta Pharmacologica Sinica》2020年第8期1041-1048,共8页中国药理学报（英文版）

基　　金：the National Natural Science Foundation of China(Grant Nos.81873732,81400917,81371250,and 81571053).

摘　　要：Paclitaxe-induced neuropathic pain(PINP)is refractory to currently used analgesics.Previous studies show a pivotal role of oxidative stressin PINP.Because the nuclear factor erythroid-2-related factor 2(Nrf2)has been considered as the critical regulator of endogenous antioxidant defense,we here explored whether activation of Nrf2 could attenuate PINP.A rat model of PINP was established by intraperitoneal injection of paclitaxel(2mg/kg)every other day with a final cumulative dose of 8 mg/kg.Hind paw withdrawal thresholds(PWTs)in response to von Frey flament stimuli were used to assess mechanicalallodynia.Weshowed that a single dose of Nf2 activator,oltipraz(10,50,and 100 mg/kg),dose-dependently attenuated established mechanical allodynia,whereas repeated injection of oltipraz(100 mg ·kg^-1·d^-1,ip.from d 14 to d 18)almost abolished the mechanical allodynia in PINP rats.The antinociceptive effect of oltipraz was blocked by pre-injection of Nf2inhibitor trigonelline(20 mg/kg,ip.).Early treatment with oltipraz(100 mg ·kg^-1·d^-1,ip.from d 0 to d 6)failed to prevent the development of the PINP,but delayed its onset.Western blot and immunofluorescence analysis revealed that the expression levels of Nf2 and HO-1 were significantly upregulated in the spinal cord of PINP rats.Repeated injection of oltipraz caused further elevation of the expression levels of Nrf2 and HO-1 in the spinal cord of PINP rats,which was reversed by pre-injection of trigonelline.These results demonstrate that oltipraz ameliorates PINP via activating Nrf2/HO-1-signaling pathway in the spinal cord.

关 键 词：PACLITAXEL neuropathic pain oxidative stress NRF2 HO-1 OLTIPRAZ 

分 类 号：R285.5[医药卫生—中药学]