Celecoxib alleviates oxaliplatin-induced hyperalgesia through inhibition of spinal ERK1/2 signaling.
Numerous pieces of evidence have revealed that oxaliplatin (OXA) evokes mechanical and cold hypersensitivity. However, the mechanism underlying these bothersome side effects needs to be further investigated. It is well known that cyclooxygenase-2 (COX-2) and extracellular signal-regulated kinases (ERK1/2) signaling play crucial roles in several pain states. Our previous data showed that Akt2 in the dorsal root ganglion (DRG) participated in the regulation of OXA-induced neuropathic pain. But it is still unclear whether spinal ERK1/2 signaling is involved in the regulation of OXA-induced hyperalgesia, and the linkage between COX-2 and ERK1/2 signaling in mediating OXA-induced hyperalgesia also remains unclear. In this research, we investigated the possible mechanism of celecoxib, a COX-2 inhibitor, in OXA-induced neuropathic pain. Our results show that single dose of OXA (12 mg/kg) significantly attenuated both the tail withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) at days 4 after the OXA treatment. Administration of celecoxib (30 mg/kg/day) for 4 and 6 days inhibited the decrease in TWL and MWT, and each was significantly higher than that of the OXA+vehicle group and was equivalent to that of the vehicles group. OXA increased the expression of cyclooxygenase-2 (COX-2) mRNA and phosphorylated extracellular signal-regulated kinase1/2 (pERK1/2) protein in the lumbar 4-5 (L4-5) spinal cord dorsal horn neurons. Administration of celecoxib for 7 days suppressed the increase in expression of COX-2 and pERK1/2 induced by OXA. Our findings suggested that COX-2 and ERK1/2 signaling in spinal cord contributed to the OXA-induced neuropathic pain.
Department of Histology and Embryology, Medical College, Nanchang University, Bayi Road 461, Nanchang 330006, China; Jiangxi Province Key Laboratory of Tumor Pathogen's and Molecular Pathology, Bayi Road 461, Nanchang 330006, China.
Hongping
H
Chen
Department of Histology and Embryology, Medical College, Nanchang University, Bayi Road 461, Nanchang 330006, China.
Qinghua
Q
Wang
Department of Histology and Embryology, Medical College, Nanchang University, Bayi Road 461, Nanchang 330006, China.
Danni
D
Shi
Department of Histology and Embryology, Medical College, Nanchang University, Bayi Road 461, Nanchang 330006, China.
Dongbo
D
Yao
Department of Histology and Embryology, Medical College, Nanchang University, Bayi Road 461, Nanchang 330006, China.
Lei
L
Zhang
Department of Human Anatomy, Medical College, Nanchang University, Bayi Road 461, Nanchang 330006, China.
Junping
J
Xiong
Department of Animal Science, Medical College, Nanchang University, Bayi Road 461, Nanchang 330006, China.
Baohua
B
Xu
celecoxib; cyclooxygenase-2; neuropathic pain; oxaliplatin; pERK1/2