Preprotachykinin A is expressed by a distinct population of excitatory neurons in the mouse superficial spinal dorsal horn including cells that respond to noxious and pruritic stimuli.
Preprotachykinin A is expressed by a distinct population of excitatory neurons in the mouse superficial spinal dorsal horn including cells that respond to noxious and pruritic stimuli.
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DOI：
10.1097/j.pain.0000000000000778
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发表时间：
2017-03
期刊：
影响因子：
7.4
通讯作者：
Todd AJ
中科院分区：
文献类型：
--
作者：
Gutierrez-Mecinas M;Bell AM;Marin A;Taylor R;Boyle KA;Furuta T;Watanabe M;Polgár E;Todd AJ
P物质前体速激肽原A的表达决定了背角浅层兴奋性神经元的独特群体，其中许多神经元对伤害性或瘙痒刺激有反应。背角浅层是伤害性和瘙痒感受性初级传入的主要靶点，含有高密度的兴奋性中间神经元。由于很难区分这些细胞中的功能群体，我们对它们在躯体感觉加工中的作用的理解一直受到限制。最近，我们根据神经降压素、神经激动素B和胃泌素释放肽的表达，在兴奋性神经元中定义了三个不重叠的群体。免疫细胞化学显示，速激肽前体蛋白(前速激肽A，PPTA)在∼的I-II板层神经元中可检测到14%，这些蛋白集中在板层II的外层。80%以上的PPTA阳性细胞缺乏转录因子Pax2(决定抑制性表型)，而这一区域的兴奋性神经元中有15%是Pax2。它们不同于神经降压素、神经激动素B或胃泌素释放肽神经元，尽管其中许多神经元含有生长抑素，生长抑素在背角浅层兴奋性中间神经元中广泛表达。我们发现，这些细胞中的许多对有害的热刺激和机械刺激以及皮内注射瘙痒原有反应。最后，我们证明这些细胞也可以在敲入Cre小鼠品系(Tac1Cre)中被识别，尽管我们的发现表明有额外的神经元群体瞬时表达PPTA。这群表达P物质的兴奋性神经元很可能在传递被认为是疼痛和瘙痒的信号方面发挥重要作用。
Expression of the substance P precursor preprotachykinin A defines a distinct population of superficial dorsal horn excitatory neurons, many of which respond to noxious or pruritic stimuli. The superficial dorsal horn, which is the main target for nociceptive and pruritoceptive primary afferents, contains a high density of excitatory interneurons. Our understanding of their roles in somatosensory processing has been restricted by the difficulty of distinguishing functional populations among these cells. We recently defined 3 nonoverlapping populations among the excitatory neurons, based on the expression of neurotensin, neurokinin B, and gastrin-releasing peptide. Here we identify and characterise another population: neurons that express the tachykinin peptide substance P. We show with immunocytochemistry that its precursor protein (preprotachykinin A, PPTA) can be detected in ∼14% of lamina I-II neurons, and these are concentrated in the outer part of lamina II. Over 80% of the PPTA-positive cells lack the transcription factor Pax2 (which determines an inhibitory phenotype), and these account for ∼15% of the excitatory neurons in this region. They are different from the neurotensin, neurokinin B, or gastrin-releasing peptide neurons, although many of them contain somatostatin, which is widely expressed among superficial dorsal horn excitatory interneurons. We show that many of these cells respond to noxious thermal and mechanical stimuli and to intradermal injection of pruritogens. Finally, we demonstrate that these cells can also be identified in a knock-in Cre mouse line (Tac1Cre), although our findings suggest that there is an additional population of neurons that transiently express PPTA. This population of substance P–expressing excitatory neurons is likely to play an important role in the transmission of signals that are perceived as pain and itch.