• Zhi-Yu Chen, Feng-Yan Shen, Lai Jiang, Xuan Zhao, Xiao-Lu Shen, Wei Zhong, Sha Liu, Zhi-Ru Wang, and Ying-Wei Wang.
• From the Department of Anesthesiology and Intensive Care Medicine, Xinhua Hospital, College of Medicine, Shanghai Jiaotong University, Shanghai, China (Z.-Y.C., F.-Y.S., L.J., X.Z., X.-L.S., Y.-W.W.); and Laboratory of Neural Circuit Plasticity & Memory, Institute of Brain Functional Genomics, East China Normal University, Shanghai, China (W.Z., S.L., Z.-R.W.).
• Anesthesiology. 2016 Jan 1; 124 (1): 169183169-83.

BackgroundSynaptic mechanisms and neuronal oscillations have been proposed to be responsible for neuropathic pain formation. Many studies have also highlighted the important role of electrical synapses in synaptic plasticity and in neuronal oscillations. Thus, electrical synapses may contribute to neuropathic pain generation. However, previous studies have primarily focused on the role of chemical synapses, while ignoring the role of electrical synapses, in neuropathic pain generation.MethodsThe authors adopted microinjection, RNA interference techniques, and behavioral tests to verify the link between connexin 36 (Cx36) and neuropathic pain. They also studied the selective Cx36 blocker mefloquine in rat chronic constriction injury and spared nerve injury model of neuropathic pain. Electrophysiologic recordings were used to further confirm the behavioral data.ResultsThe authors found that Cx36, which constitutes the neuron-neuron electrical synapses, was up-regulated in the anterior cingulate cortex after nerve injury (n = 5). Meanwhile, Cx36-mediated neuronal oscillations in the gamma frequency range (30 to 80 Hz) (n = 7 to 8) and the neuronal synaptic transmission (n = 13 to 19) were also enhanced. Neuropathic pain was relieved by disrupting Cx36 function or expression in the anterior cingulate cortex. They also found that mefloquine, which are clinically used for treating malaria, affected gamma oscillations and synaptic plasticity, leading to a sustained pain relief in chronic constriction injury and spared nerve injury models (n = 7 to 12).ConclusionThe electrical synapses blocker mefloquine could affect gamma oscillations and synaptic plasticity in the anterior cingulate cortex and relieve neuropathic pain. Cx36 may be a new therapeutic target for treating chronic pain.

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