Wan Li, Jin Hua, Liu Xian-Yu, Jeffry Joseph, Barry Devin M, Shen Kai-Feng, Peng Jia-Hang, Liu Xue-Ting, Jin Jin-Hua, Sun Yu, Kim Ray, Meng Qing-Tao, Mo Ping, Yin Jun, Tao Ailin, Bardoni Rita, Chen Zhou-Feng
Center for the Study of Itch, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Sci Rep. 2017 Nov 13;7(1):15466. doi: 10.1038/s41598-017-15756-0.
A key question in our understanding of itch coding mechanisms is whether itch is relayed by dedicated molecular and neuronal pathways. Previous studies suggested that gastrin-releasing peptide (GRP) is an itch-specific neurotransmitter. Neuromedin B (NMB) is a mammalian member of the bombesin family of peptides closely related to GRP, but its role in itch is unclear. Here, we show that itch deficits in mice lacking NMB or GRP are non-redundant and Nmb/Grp double KO (DKO) mice displayed additive deficits. Furthermore, both Nmb/Grp and Nmbr/Grpr DKO mice responded normally to a wide array of noxious stimuli. Ablation of NMBR neurons partially attenuated peripherally induced itch without compromising nociceptive processing. Importantly, electrophysiological studies suggested that GRPR neurons receive glutamatergic input from NMBR neurons. Thus, we propose that NMB and GRP may transmit discrete itch information and NMBR neurons are an integral part of neural circuits for itch in the spinal cord.
在我们对瘙痒编码机制的理解中，一个关键问题是瘙痒是否通过专门的分子和神经元通路进行传递。先前的研究表明，胃泌素释放肽（GRP）是一种瘙痒特异性神经递质。神经介素B（NMB）是与GRP密切相关的蛙皮素家族肽的哺乳动物成员，但其在瘙痒中的作用尚不清楚。在这里，我们表明，缺乏NMB或GRP的小鼠的瘙痒缺陷并非冗余，Nmb/Grp双敲除（DKO）小鼠表现出累加缺陷。此外，Nmb/Grp和Nmbr/Grpr DKO小鼠对多种有害刺激均有正常反应。NMBR神经元的消融部分减弱了外周诱导的瘙痒，而不影响伤害性处理。重要的是，电生理研究表明，GRPR神经元接受来自NMBR神经元的谷氨酸能输入。因此，我们提出NMB和GRP可能传递离散的瘙痒信息，并且NMBR神经元是脊髓中瘙痒神经回路的一个组成部分。
