Almost over 140 non-olfactory G protein-coupled receptors (GPCRs) have no known endogenous or synthetic ligands, or for which understanding of their physiological function is still elusive; these are referred to as orphan GPCRs. In the dorsal root ganglion (DRG) or spinal cord, several orphan GPCRs are expressed that can regulate neuropathic pain. Notably, one of the orphan GPCRs, GPR151, is upregulated in the habenular, presynaptic area, trigeminal ganglion, non-peptidergic C-fibre DRG, and dorsal horn spinal cord after nerve injury. Despite the lack of ligands, GPR151 has been reported as a novel therapeutic target for the treatment of neuropathic pain.