In this study, we develop two cell‐permeable, high‐affinity inhibitors, Tat‐C5 and Tat‐P4‐(C5)2, of the PICK1 PDZ domain with the purpose of disrupting the interaction of PICK1 with AMPARs and thereby reverse central sensitization and its related maladaptive plasticity believed to be associated with neuropathic pain. This evidence concerns the gene PICK1 and Pain.