Neuropathic pain is a chronic disease with hallmarks such as chronic allodynia and hyperalgesia. Previous studies have shown that the transforming growth factor-β superfamily acts as a protecting factor against neuropathic pain. In the current study, we found that growth and differentiation factor 10 (GDF10), which belongs to the transforming growth factor-β superfamily, is mainly expressed in the superficial layers of spinal dorsal horn neurons and it was dramatically downregulated after spinal nerve ligation and N-methyl-D-aspartate (NMDA) intrathecal infusion. Moreover, the decrease in GDF10 expression and increase in mechanical sensitivity could be blocked by MK-801, an antagonist of the NMDA receptor. These results suggest that the decreasing GDF10 may contribute toward neuropathic pain by facilitating NMDA receptor activation. Our findings shed new light on the understanding of the molecular mechanisms underlying neuropathic pain.