Abstract:Objective:This study aimed to investigate the antinociceptive effect of growth differentiation factor 15(GDF-15)and its possible mechanism. Methods:Intrathecal injection of GDF-15 (50 ng) was given for formalin–induced pain model test and different dose groups were set up with intraperitoneal injection of GDF-15 (10 μg/kg, 30 μg/kg and 100 μg/kg) to perform a formalin–induced pain model test. The formalin pain threshold was compared with vehicle control group to measure the analgesic effect. Western blot and immunofluorescence experiments were used to test the expression of GDF-15’s specific receptor GFRAL. Real-time PCR was used to measure the mRNA expression of IL-6, IL-1β, TNF-α, PDYN and PENK in the spinal cord of formalin mice (50 ng). Results:The results showed that both intrathecal and intraperitoneal administration demonstrated that GDF-15 had a antinociceptive effect on inflammatory pain and the antinociceptive effect of intraperitoneal administration was dose-dependent, while there was no significant effect on acute pain. The specific receptor of GDF-15, GFRAL, was expressed in the brain, cerebellum and spinal cord, and it only expressed in neurons in the spinal cord dorsal horn. Also, we found that intrathecal injection of GDF-15 can inhibit the expression of pro-inflammatory factors IL-6 and TNF-α in the spinal cord of formalin mice. Conclusion: GDF-15 has a antinociceptive effect on formalin-induced inflammatory pain and its possible mechanism is by reducing the expression of pro-inflammatory factors IL-6 and TNF-α.