Ca²⁺ / calmodulin-dependent protein kinase II (CaMKII) is a multifunctional serine/ threonine proteinkinase in a large number of neurons and is widely involved in pain modulation. Neuropathic pain is chronic refractory paincaused by disease or damage to the somatosensory system. CaMKII plays an important role in the occurrence anddevelopment of various types of neuropathic pain such as central, peripheral, diabetic and drug-induced neuropathic pain.This review focuses on the regulation of CaMKII-mediated neuropathic pain and its upstream and downstream pathways to provide a reference for the future study of CaMKII in the field of neuropathic pain.