西亚试剂：Alleviating Neuropathic Pain Hypersensitivity by Inhibiting

Alleviating Neuropathic Pain Hypersensitivity by Inhibiting PKMζ in the Anterior Cingulate Cortex

Xiang-Yao Li1,2,*, Hyoung-Gon Ko3,*, Tao Chen1,2,*, Giannina Descalzi1, Kohei Koga1, Hansen Wang1, Susan S. Kim1, Yuze Shang1, Chuljung Kwak3, Soo-Won Park3, Jaehoon Shim2,3, Kyungmin Lee3,4, Graham L. Collingridge2,5, Bong-Kiun Kaang2,3,? and Min Zhuo1,2,?

Abstract

Synaptic plasticity is a key mechanism for chronic pain. It occurs at different levels of the central nervous system, including spinal cord and cortex. Studies have mainly focused on signaling proteins that trigger these plastic changes, whereas few have addressed the maintenance of plastic changes related to chronic pain. We found that protein kinase M zeta (PKMζ) maintains pain-induced persistent changes in the mouse anterior cingulate cortex (ACC). Peripheral nerve injury caused activation of PKMζ in the ACC, and inhibiting PKMζ by a selective inhibitor, ζ-pseudosubstrate inhibitory peptide (ZIP), erased synaptic potentiation. Microinjection of ZIP into the ACC blocked behavioral sensitization. These results suggest that PKMζ in the ACC acts to maintain neuropathic pain. PKMζ could thus be a new therapeutic target for treating chronic pain.