• Shi-Hao Gao, Lin-Lin Shen, Hui-Zhong Wen, Yan-Dong Zhao, and Huai-Zhen Ruan.
• From the Department of Neurobiology, College of Basic Medical Science, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing, China (S.-H.G., H.-Z.W., Y.-D.Z., H.-Z.R.); and Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing, China (L.-L.S.).
• Anesthesiology. 2017 Sep 1; 127 (3): 515-533.

BackgroundInhibition of the metabotropic glutamate receptor subtype 1 in the anterior cingulate cortex has an analgesic effect during sustained nociceptive hypersensitivity. However, the specific changes in different subtypes of anterior cingulate cortex layer 5 pyramidal neurons, as well as the distinct effect of metabotropic glutamate receptor subtype 1 inhibition on different neuronal subtypes, have not been well studied.MethodsRetrograde labeling combined with immunofluorescence, whole cell clamp recording, and behavioral tests combined with RNA interference were performed in a rat model of chronic constriction injury to the sciatic nerve.ResultsCommissural layer 5 pyramidal neurons (projecting to the contralateral cortex) existed in the anterior cingulate cortex. The voltage-gated potassium channel subunit 2-mediated current in these neurons were substantially reduced after chronic constriction injury (current densities at +30 mV for the sham, and chronic constriction injury neurons were [mean ± SD] 10.22 ± 3.42 pA/pF vs. 5.58 ± 2.71 pA/pF, respectively; n = 11; P < 0.01), which increased the spike width and fast afterhyperpolarization potential, resulting in hyperexcitability. Inhibition of metabotropic glutamate receptor subtype 1 alleviated the down-regulation of voltage-gated potassium channel subunit 2 currents (current density increased by 8.11 ± 3.22 pA/pF; n = 7; P < 0.01). Furthermore, knockdown of voltage-gated potassium channel subunit 2 current in the commissural neurons attenuated the analgesic effect of metabotropic glutamate receptor subtype 1 inhibition (n = 6 rats; P < 0.05).ConclusionsThe effect of metabotropic glutamate receptor subtype 1 inhibition on commissural anterior cingulate cortex layer 5 pyramidal neurons is likely different with the modification of previously studied hyperpolarization-activated/cyclic nucleotide-gated channel-dependent neurons but relies on the alteration of voltage-gated potassium channel subunit 2 currents. These results will contribute to a better understanding of the therapeutic role of metabotropic glutamate receptor subtype 1 in chronic pain.

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