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Oxaliplatin (OXL) is a third-generation chemotherapeutic agent commonly used to treat metastatic digestive
tumors; however, one of the main limiting complications of OXL is neuropathic pain. In this study, the underlying
mechanisms responsible for OXL evoked-neuropathic pain were examined. Using a rat model, the results
demonstrated that intraperitoneal (i.p.) injection of OXL significantly increased mechanical pain and cold
sensitivity as compared with control animals (P < 0.05 vs. control rats). Blocking proteinase-activated receptor
2 (PAR2) significantly attenuated mechanical pain and cold sensitivity observed in control rats and OXL rats (P <
0.05 vs. vehicle control). The attenuating effect of PAR2 on mechanical pain and cold sensitivity were significantly
smaller in OXL-rats than in control rats. The role played by PAR2 downstream signaling pathways [namely,
transient receptor potential ankyrin 1 (TRPA1)] in regulating OXL evoked-neuropathic pain was also examined.
The data shows that TRPA1 expression was upregulated in the lumbar dorsal root ganglion (DRG) of OXL rats and
blocking TRPA1 inhibited mechanical pain and heightened cold sensitivity (P <0.05 vs. control rats). Blocking
PAR2 also significantly decreased TRPA1expression in the DRG. Findings in this study show that OXL intervention
amplifies mechanical hyperalgesia and cold hypersensitivity and PAR2 plays an important role in regulating OXLinduced
neuropathic pain via TRPA1 pathways.