研究揭示感知觸摸和疼痛的脊髓通路
作者：
小柯機器人發布時間：2020/10/31 21:37:40
近日，美國霍華德休斯醫學研究所David D. Ginty及其研究組揭示感知觸摸和疼痛的脊髓通路。相關論文於2020年10月28日在線發表於國際學術期刊《自然》。
研究人員發現了兩個表達結構相關的G蛋白偶聯受體（GPCR）TACR1和GPR83的投射神經元形成平行上升迴路模塊，這些模塊協作將熱、觸覺和有害的皮膚信號從脊髓傳遞至腦橋側臂旁核。在此核內，表達Tacr1或Gpr83的SPB（spinoparabrachial ）神經元軸突支配不同的亞核群體，並且強烈的光遺傳學刺激軸突末端誘導了不同的逃避行為和自主反應。此外，表達Gpr83的SPB神經元對皮膚機械刺激高度敏感，並從高閾值和低閾值的原代機械感覺神經元中接收強大的突觸輸入。
值得注意的是，取決於刺激強度，與表達Gpr83的SPB神經元激活相關的化合價可以是正值或負值。這些發現揭示了SPB的解剖、生理和功能上不同的細分，是觸覺和疼痛的感知基礎。
據悉，前外側通路由上升的脊髓束組成，這些脊髓束將疼痛、溫度和觸覺信息從脊髓傳遞到大腦。前外側通路的投射神經元是疼痛治療的潛在目標，因為從周圍散發的傷害感受信號通過這些脊柱投射神經元傳導至大腦。但是，前外側通路的組織邏輯仍然知之甚少。
附：英文原文
Title: Parallel ascending spinal pathways for affective touch and pain
Author: Seungwon Choi, Junichi Hachisuka, Matthew A. Brett, Alexandra R. Magee, Yu Omori, Noor-ul-Aine Iqbal, Dawei Zhang, Michelle M. DeLisle, Rachel L. Wolfson, Ling Bai, Celine Santiago, Shiaoching Gong, Martyn Goulding, Nathaniel Heintz, H. Richard Koerber, Sarah E. Ross, David D. Ginty
Issue&Volume: 2020-10-28
Abstract: The anterolateral pathway consists of ascending spinal tracts that convey pain, temperature and touch information from the spinal cord to the brain1–4. Projection neurons of the anterolateral pathway are attractive therapeutic targets for pain treatment because nociceptive signals emanating from the periphery are channelled through these spinal projection neurons en route to the brain. However, the organizational logic of the anterolateral pathway remains poorly understood. Here we show that two populations of projection neurons that express the structurally related G-protein-coupled receptors (GPCRs) TACR1 and GPR83 form parallel ascending circuit modules that cooperate to convey thermal, tactile and noxious cutaneous signals from the spinal cord to the lateral parabrachial nucleus of the pons. Within this nucleus, axons of spinoparabrachial (SPB) neurons that express Tacr1 or Gpr83 innervate distinct sets of subnuclei, and strong optogenetic stimulation of the axon terminals induces distinct escape behaviours and autonomic responses. Moreover, SPB neurons that express Gpr83 are highly sensitive to cutaneous mechanical stimuli and receive strong synaptic inputs from both high- and low-threshold primary mechanosensory neurons. Notably, the valence associated with activation of SPB neurons that express Gpr83 can be either positive or negative, depending on stimulus intensity. These findings reveal anatomically, physiologically and functionally distinct subdivisions of the SPB tract that underlie affective aspects of touch and pain. Two populations of neurons with distinct anatomy and receptor expression that convey information from the spinal cord to the brain have different functional properties with respect to touch and pain.
DOI: 10.1038/s41586-020-2860-1
Source: https://www.nature.com/articles/s41586-020-2860-1