Abstract: Objective To observe the therapeutic effect of metformin on pathological pain in mice with radiation dermatitis and explore the underlying mechanism. Methods Thirty- two male adult ICR mice were randomized into normal control group, radiation dermatitis model group, metformin treatment (200 mg/kg) group and gabapentin (100 mg/kg) group (n=8). In the latter two groups, metformin treatment was administered after modeling via intraperitoneal injection and gabapentin by gavage on a daily basis for 16 days; the mice in the control group and model group received intraperitoneal injection of normal saline. After the last administration, radiation dermatitis was graded in each group. Mechanical withdraw threshold (MWT) and thermal withdrawal latency (TWL) of the mice were tested one day before and at 1, 4, 8, 12 and 16 days after modeling. Western blotting was used to measure the protein expression levels of p38MAPK, p-p38MAPK, NF-κB p65 and p-NF-κB p65 in the L4-L6 spinal cord, and the concentrations of IL-1β, IL-6 and TNF-α in the spinal cord tissue were determined with ELISA. Results Compared with those in the control group, the mice in the other 3 groups showed obvious symptoms of radiation dermatitis after modeling (P<0.05), which were significantly alleviated by treatment with metformin (P<0.05). The mice in the model group exhibited significant decreases in MWT and TWL (P<0.05), which were improved by treatment with metformin and gabapentin (P<0.05). Compared with those in the model group, the levels of p-p38MAPK, p-NF-κB p65, IL-1β, IL-6 and TNF-α in the spinal cord were significantly decreased in the mice after metformin treatment (P<0.05). Conclusion Metformin can significantly ameliorate pathological pain symptoms in mice with radiation dermatitis possibly by inhibiting the activation of p38MAPK/NF-κB signaling pathway.

Key words: metformin; radiation dermatitis; pathological pain; p38MAPK; nuclear factor-κB