Send to

Choose Destination
Science. 2010 Dec 3;330(6009):1400-4. doi: 10.1126/science.1191792.

Alleviating neuropathic pain hypersensitivity by inhibiting PKMzeta in the anterior cingulate cortex.

Author information

Department of Physiology, Faculty of Medicine, Center for the Study of Pain, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.


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.

[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center