Paclitaxel is used for the treatment of several types of cancers.
However, one of the significant limiting complications of
paclitaxel is painful peripheral neuropathy during its therapy. In
this study we examined the engagement of antioxidative signal
pathway of the dorsal root ganglion (DRG) in mechanical and
thermal hypersensitivity evoked by paclitaxel. Behavioral test was
performed to determine mechanical and thermal sensitivity in
rats. Western blot analysis and ELISA were used to examine
expression of Nrf2-antioxidant response element (ARE) and
superoxide dismutases (SOD); and the levels of products of
oxidative stress in the DRG. Our results show that paclitaxel
increased mechanical and thermal sensitivity as compared with
vehicle control animals. Paclitaxel also impaired Nrf2-ARE and
SOD in the DRG and amplified products of oxidative stress,
namely 8-isoprostaglandin F2α and 8-hydroxy-2’-
deoxyguanosine. Systemic administration of SOD mimetic using
tempol, antioxidant vitamin C or blocking oxidative pathway
using NADPH oxidase inhibitor (GKT137831) attenuated
mechanical and thermal hypersensitivity induced by paclitaxel.
This inhibitory effect was accompanied with decreases of
proinflammatory cytokines (PICs) such as IL-1β, IL-6 and TNF-α
in the DRG. In conclusion, the data revealed impairment of
Nrf2-ARE and heightened oxidative and PIC signals in the DRG of
paclitaxel rats, leading to neuropathic pain. Balancing of reactive
oxygen species by supplying antioxidants and/or inhibiting
NADPH oxidase appears significant to yield beneficial effects in
neuropathic pain conditions after chemotherapeutic paclitaxel.