Knockdown of PSD-95/SAP90 delays the development of neuropathic pain in rats.

Our previous work has shown that PSD-95/SAP90 is required for NMDA receptor-mediated thermal hyperalgesia. To address the role of PSD-95/SAP90 in chronic pain, the present study investigated the effect of the deficiency of PSD-95/SAP90 on nerve injury-induced neuropathic pain. Following unilateral L5 spinal nerve injury, mechanical and thermal hyperalgesia developed within 3 days and persisted for 9 days or longer on the injured side. The intrathecal administration of antisense oligodeoxynucleotide specifically against PSD-95/SAP90, but not sense or missense oligodeoxynucleotide, dose-dependently delayed the onset of tactile allodynia and thermal hyperalgesia. These results suggest that PSD-95/SAP90 might be involved in the central mechanisms of the development of chronic neuropathic pain.