【摘 要】
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Objective Reactive oxygen species (ROS) such as superoxide are emerging as important signaling molecules in physiological plasticity but also in peripheral and spinal cord pain pathology.Underlying me
【机 构】
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Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders, Tangdu Hospi
【出 处】
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中国神经科学学会第九届全国学术会议暨第五届会员代表大会
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Objective Reactive oxygen species (ROS) such as superoxide are emerging as important signaling molecules in physiological plasticity but also in peripheral and spinal cord pain pathology.Underlying mechanisms and pain-related ROS signaling in the brain remain to be determined.Neuroplasticity in the amygdala plays a key role in emotional-affective pain responses and depends on group Ⅰ metabotropic glutamate receptors (mGluRs) and protein kinases.Methods Using patch-clamp, live-cell imaging, and behavioral assays, we tested the hypothesis that mitochondrial ROS links group Ⅰ mGluRs to protein kinase activation to increase neuronal excitability and pain behavior.Results Agonists for mGluR1/5 (DHPG) or mGluR5 (CHPG) increased neuronal excitability of neurons in the laterocapsular division of the central nucleus of the amygdala (CeLC).DHPG effects were inhibited by an mGluR5 antagonist (MTEP), IP3 receptor blocker (xestospongin C), or ROS scavengers (PBN, Tempol), but not by an mGluR1 antagonist (LY367385) or NO synthase inhibitor (L-NAME).Tempol inhibited the effectsof IP3 but not those of a PKC activator, indicating that ROS activation was IP3 mediated.Live-cell imaging in CeLC-containing brain slices directly showed DHPG-induced and synaptically evoked mitochondrial superoxide production.DHPG also increased pain-related vocalizations and spinal reflexes through a mechanism that required mGluR5, IP3, and ROS.Combined application of inhibitors of ERK (U0126) and PKA (KT5720) was necessary to block completely the excitatory effects of a ROS donor (tBOOH).A PKC inhibitor (GF 109203X) had no effect.Antagonists and inhibitors alone did not affect neuronal excitability.Conclusion The results suggest an important role for the novel mGluR5-IP3-ROS-ERK/PKA signaling pathway in amygdala pain mechanisms.
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