Cho Pyung Sun, Lee Han Kyu, Choi Young In, Choi Seung In, Lim Ji Yeon, Kim Minseok, Kim Hyun, Jung Sung Jun, Hwang Sun Wook
Department of Biomedical Sciences, College of Medicine, Korea University, Seoul 02841, Korea.
Department of Physiology, College of Medicine, Korea University, Seoul 02841, Korea.
Biomedicines. 2021 Mar 5;9(3):256. doi: 10.3390/biomedicines9030256.
Modulation of the function of somatosensory neurons is an important analgesic strategy, requiring the proposal of novel molecular targets. Many G-protein-coupled receptors (GPRs) have been deorphanized, but the receptor locations, outcomes due to their activations, and their signal transductions remain to be elucidated, regarding the somatosensory nociceptor function. Here we report that GPR171, expressed in a nociceptor subpopulation, attenuated pain signals via Gi/o-coupled modulation of the activities of nociceptive ion channels when activated by its newly found ligands. Administration of its natural peptide ligand and a synthetic chemical ligand alleviated nociceptor-mediated acute pain aggravations and also relieved pathologic pain at nanomolar and micromolar ranges. This study suggests that functional alteration of the nociceptor neurons by GPR171 signaling results in pain alleviation and indicates that GPR171 is a promising molecular target for peripheral pain modulation.
调节体感神经元的功能是一种重要的镇痛策略，这需要提出新的分子靶点。许多G蛋白偶联受体（GPR）已被明确功能，但关于体感伤害感受器功能，其受体位置、激活后的结果及其信号转导仍有待阐明。在此我们报告，在伤害感受器亚群中表达的GPR171，在被其新发现的配体激活时，通过Gi/o偶联调节伤害性离子通道的活性来减弱疼痛信号。给予其天然肽配体和一种合成化学配体可减轻伤害感受器介导的急性疼痛加剧，并且在纳摩尔和微摩尔范围内也可缓解病理性疼痛。这项研究表明，GPR171信号传导引起的伤害感受器神经元功能改变可减轻疼痛，并表明GPR171是外周疼痛调节的一个有前景的分子靶点。
