Publication Date:
2010-12-04
Description:
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 (PKMzeta) maintains pain-induced persistent changes in the mouse anterior cingulate cortex (ACC). Peripheral nerve injury caused activation of PKMzeta in the ACC, and inhibiting PKMzeta by a selective inhibitor, zeta-pseudosubstrate inhibitory peptide (ZIP), erased synaptic potentiation. Microinjection of ZIP into the ACC blocked behavioral sensitization. These results suggest that PKMzeta in the ACC acts to maintain neuropathic pain. PKMzeta could thus be a new therapeutic target for treating chronic pain.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Xiang-Yao -- Ko, Hyoung-Gon -- Chen, Tao -- Descalzi, Giannina -- Koga, Kohei -- Wang, Hansen -- Kim, Susan S -- Shang, Yuze -- Kwak, Chuljung -- Park, Soo-Won -- Shim, Jaehoon -- Lee, Kyungmin -- Collingridge, Graham L -- Kaang, Bong-Kiun -- Zhuo, Min -- CIHR66975/Canadian Institutes of Health Research/Canada -- CIHR84256/Canadian Institutes of Health Research/Canada -- G0601813/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2010 Dec 3;330(6009):1400-4. doi: 10.1126/science.1191792.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉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.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21127255" target="_blank"〉PubMed〈/a〉
Keywords:
Adenylyl Cyclases/genetics/metabolism
;
Analgesics/administration & dosage/pharmacology
;
Animals
;
Enzyme Inhibitors/administration & dosage/*pharmacology
;
Excitatory Postsynaptic Potentials/drug effects
;
Gyrus Cinguli/*enzymology/physiology
;
Long-Term Potentiation
;
Male
;
Memory/drug effects
;
Mice
;
Mice, Inbred C57BL
;
Mice, Transgenic
;
Neuralgia/*drug therapy/*enzymology
;
Patch-Clamp Techniques
;
Peptides/administration & dosage/*pharmacology
;
Peroneal Nerve/injuries
;
Phosphorylation
;
Protein Kinase C/*antagonists & inhibitors/*metabolism
;
Receptors, AMPA/metabolism
;
Sensory Receptor Cells/physiology
;
Somatosensory Cortex/physiology
;
Synapses/physiology
;
Synaptic Transmission
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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