Mounting evidence suggest that PD-L1/PD-1 pathway of DRG, sciatic nerve, and spinal cord dorsal horn (SDH) plays an important role in various pain models, including acute pain [19, 47], inflammatory pain [34, 37], neuropathic pain [16–18, 48–50], and cancer pain [19, 35, 51].(Table 1) The increased expression of PD-L1/PD-1 pathway in trigeminal ganglia neurons and DRG neurons impedes migraine-like pain and formalin-induced acute inflammatory pain [19, 47]. This evidence concerns the gene CD274 and cancer.