Alleviating Neuropathic Pain Hypersensitivity by Inhibiting PKMζ in the Anterior Cingulate Cortex
Alleviating Neuropathic Pain Hypersensitivity by Inhibiting PKMζ in the Anterior Cingulate Cortex
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DOI：
10.1126/science.1191792
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发表时间：
2010-12-03
期刊：
影响因子：
56.9
通讯作者：
Zhuo, Min
中科院分区：
文献类型：
--
作者：
Li, Xiang-Yao;Ko, Hyoung-Gon;Zhuo, Min
突触可塑性是慢性疼痛的关键机制。它发生在中枢神经系统的不同层次，包括脊髓和皮质。研究主要集中在触发这些塑料变化的信号蛋白，而很少有人解决与慢性疼痛相关的塑料变化的维持。我们发现蛋白激酶M ζ（PKM zeta）维持小鼠前扣带皮层（ACC）疼痛诱导的持续性变化。周围神经损伤引起ACC中PKM zeta的激活，并且通过选择性抑制剂zeta-假底物抑制肽（ZIP）抑制PKM zeta，消除突触增强。向ACC微量注射ZIP可阻断行为敏感化。这些结果表明，PKM zeta在ACC的行为，以维持神经病理性疼痛。因此，PKM zeta可能成为治疗慢性疼痛的新靶点。
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 (PKM zeta) maintains pain-induced persistent changes in the mouse anterior cingulate cortex (ACC). Peripheral nerve injury caused activation of PKM zeta in the ACC, and inhibiting PKM zeta 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 PKM zeta in the ACC acts to maintain neuropathic pain. PKM zeta could thus be a new therapeutic target for treating chronic pain.