Background　Postsynaptic density(PSD), a dense anchoring and scaffolding protein, plays a critical role in regulating the interactions between glutamate receptors and associated signaling enzymes.　Objective　To illuminate the role and mechanism of PSD in the development and progression of pathological pain.　Content　This paper overview recent progresses of research in the mechanism of PSD-95, Homer and Shank proteins, three major scaffolding molecules at PSD in chronic neuropathic pain(NPP), inflammatory and cancer pain.　Trend　Here, we provide new information related to the role of PSD scaffolding protein in the targeted clinical therapy of neural pathological pain.