Melanocortin-4 receptor in subthalamic nucleus is involved in the modulation of nociception.

IF 1.4 Q4 IMMUNOLOGY American journal of clinical and experimental immunology Pub Date : 2018-08-20 eCollection Date: 2018-01-01
Dong-Ji Han, Zhi-Gang He, Hui Yang
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Abstract

Deep brain stimulation of the subthalamic nucleus (STN-DBS) stimulation produces significant improvement of overall pain related to Parkinson disease; however, the mechanisms underlying analgesic effects of STN-DBS are still unknown. This report describes direct neuroanatomical evidence for the central melanocortinergic-opioidergic circuits in the STN. We investigated melanocortin-4 receptor (MC4R) and mu-opioid receptor (MOR)-positive expression of the STN in MC4R-GFP transgenic mice using fluorescence immunohistochemical detection. Immunohistochemistry showed a large number of MC4R-GFP- and MOR-positive neurons within the STN region, and approximately 50% of MC4R-GFP-positive neurons coexpressed MOR. The results of this study showed direct neuroanatomical evidence for the central melanocortinergic-opioidergic signaling in the STN region. These findings contribute to the view of melanocortinergic-opioidergic circuits in the subthalamic nucleus as a reliable source of modulating of nociception with therapeutic potential for alleviating pain.

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丘脑下核黑素皮质素-4受体参与伤害感觉的调节。
丘脑底核深部脑刺激(STN-DBS)刺激可显著改善帕金森病相关的整体疼痛;然而,STN-DBS镇痛作用的机制尚不清楚。本报告描述了STN中中枢黑素皮质能-阿片能回路的直接神经解剖学证据。采用荧光免疫组化方法研究了MC4R- gfp转基因小鼠中黑素皮质素-4受体(melanocortin-4 receptor, MC4R)和阿片受体(mua -opioid receptor, MOR) STN的阳性表达。免疫组化显示STN区有大量MC4R-GFP和MOR阳性神经元,约50%的MC4R-GFP阳性神经元共表达MOR。本研究结果为STN区域的中枢黑素皮质能-阿片能信号传导提供了直接的神经解剖学证据。这些发现有助于认为,丘脑下核中的黑素皮质能-阿片能回路是调节伤害感觉的可靠来源,具有减轻疼痛的治疗潜力。
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