Alleviating neuropathic pain hypersensitivity by inhibiting PKMζ in the anterior cingulate cortex

Xiang Yao Li, Hyoung Gon Ko, Tao Chen, Giannina Descalzi, Kohei Koga, Hansen Wang, Susan S. Kim, Yuze Shang, Chuljung Kwak, Soo Won Park, Jaehoon Shim, Kyungmin Lee, Graham L. Collingridge, Bong Kiun Kaang, Min Zhuo

Research output: Contribution to journalArticlepeer-review

346 Scopus citations

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.

Original languageEnglish
Pages (from-to)1400-1404
Number of pages5
JournalScience
Volume330
Issue number6009
DOIs
StatePublished - 3 Dec 2010

Fingerprint

Dive into the research topics of 'Alleviating neuropathic pain hypersensitivity by inhibiting PKMζ in the anterior cingulate cortex'. Together they form a unique fingerprint.

Cite this