To investigate the effects of intrathecally administered U0126 on the expression of Nav1.7 protein in dorsal root ganglia and changes in mechanical hyperalgesia in a rat model of paclitaxel-induced neuropathic pain.

Adult male SD rats were used. The experiment was performed in 2 parts. In part one, 36 rats were randomly divided into 2 groups (n=18 each): paclitaxel group (group P) and control group (group vehicle). Neuropathic pain was produced by intraperitoneal injection of paclitaxel (2 mg/kg every other day for 4 times) in group P. In part two, a micro-catheter was inserted into sbarachnoid space with the tip positioned at lumbar segment of spinal cord in all animals. Twelve rats were randomly divided into 2 groups (n=6 each): U0126 group and dimethylsurfoxide (DMSO) group. Mechanical paw withdrawal latency (PWT) was measured. Then the rats were sacrificed and the L4-L6 segments of dorsal root ganglion (DRG) were removed for determination of extracellular regulated protein kinases 1/2 (ERK1/2) and Nav1.7 expression by Western blotting.

As compared with group vehicle (60±5, 59±4, 65 ±4, 2.13±0.09, 2.41±0.07, 2.56±0.05, 0.41±0.03, 0.44±0.06, and 0.43±0.05), PWT was significantly decreased 7 to 21 days after administration, and the expression of ERK1/2 and Nav1.7 in DRG was up-regulated in group P (53±4, 49±5, 51±3, 4.14±0.10, 4.50±0.08, 4.32±0.09, 0.65±0.05, 0.67±0.04, and 0.59±0.03; P<0.05 or 0.01). Intrathecal U0126 1 μg significantly decreased the PWT induced by paclitaxel injection and attenuated the expression of phosphorylated ERK1/2 and Nav1.7 in DRG (48±3, 3.81±0.08, 0.81±0.04 vs. 54±4, 1.94±0.09, 0.56±0.04; P<0.05).

ERK1/2 signaling pathway mediates paclitaxel-induced neuropathic pain, and the mechanism is likely related to the increase in the Nav1.7 expression in DRG.

Sodium channels; Paclitaxel; Neuralgia; Spinal