The pathophysiology of neuropathic pain is very complex. It involves several environmental and central mechanisms. In this study, we tried to assess the modulatory effect of (S)-3,4-Dicarboxyphenylglycine (DCPG), a metabotropic glutamate receptor subtype 8 (mGluR8) agonist, in a model of chronic central neuropathic pain in male rats. We used a spinal cord contusion method (T6-T8) for the induction of chronic central neuropathic pain.Male Wistar rats were randomly assigned to 5 equal groups (n = 10 per group). Clips compression injury model was used to induce chronic central neuropathic pain. Three weeks after spinal cord injury DCPG, siRNA and normal saline were administered intra-ventrolaterally to the periaqueductal gray (PAG) region. Paw withdrawal response to acetone (cold allodynia) was assessed through acetone test. In addition, the effects of DCPG on rostral ventromedial medulla (RVM) off-cells activity were evaluated with immunohistochemistry. mGluR8 expressions were also measured.We found that treatment with DCPG increased pain threshold in acetone test. In addition, immunohistochemical evaluation of RVM off-cells showed that DCPG increased the suppressive function of these cells.The results revealed that activation of mGluR8 in PAG is capable to improve pain threshold via modulation of RVM off-cells activity. SCI: spinal cord injury; DCPG: (S)-3,4-dicarboxyphenylglycine; PAG: periaqueductal gray; siRNA: small interfering ribonucleic acid; RVM: rostral ventromedial medulla; mGluR: metabotropic glutamate receptor.