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Nrf2 activation ameliorates mechanical allodynia in paclitaxel-induced neuropathic pain

   
@article{APS10180,
	author = {Ya-qun Zhou and Dai-qiang Liu and Shu-ping Chen and Nan Chen and Jia Sun and Xiao-mei Wang and Fei Cao and Yu-ke Tian and Da-wei Ye},
	title = {Nrf2 activation ameliorates mechanical allodynia in paclitaxel-induced neuropathic pain},
	journal = {Acta Pharmacologica Sinica},
	volume = {41},
	number = {8},
	year = {2020},
	keywords = {},
	abstract = {Paclitaxel-induced neuropathic pain (PINP) is refractory to currently used analgesics. Previous studies show a pivotal role of oxidative stress in 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 (2 mg/kg) every other day with a final cumulative dose of 8 mg/kg. Hind paw withdrawal thresholds (PWTs) in response to von Frey filament stimuli were used to assess mechanical allodynia. We showed that a single dose of Nrf2 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, i.p. 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 Nrf2 inhibitor trigonelline (20 mg/kg, i.p.). Early treatment with oltipraz (100 mg· kg−1· d−1, i.p. 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 Nrf2 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.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/10180}
}