A central role for spinal dorsal horn neurons that express neurokinin-1 receptors in chronic itch.
A central role for spinal dorsal horn neurons that express neurokinin-1 receptors in chronic itch.
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DOI：
10.1097/j.pain.0000000000000172
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发表时间：
2015-07
期刊：
影响因子：
7.4
通讯作者：
Carstens E
中科院分区：
文献类型：
--
作者：
Akiyama T;Nguyen T;Curtis E;Nishida K;Devireddy J;Delahanty J;Carstens MI;Carstens E
我们研究了表达神经激肽-1受体（NK 1 R）和/或胃泌素释放肽受体（GRPR）的脊髓神经元在卵清蛋白（OVA）诱导的慢性特应性皮炎（AD）小鼠模型中的作用。接受反复局部应用OVA的小鼠表现出过敏样皮肤病变和慢性瘙痒的行为体征，包括自发性抓挠、触摸诱发的抓挠（触觉异常）和氯喹诱发的抓挠（触觉过度）的增强。鞘内注射P物质-皂草素（SP-SAP）和蛙皮素-皂草素（BB-SAP）到OVA致敏小鼠中，以分别神经毒性地消融表达NK 1 R或GRPR的脊髓神经元。SP-SAP可降低脊髓背角浅层NK 1 R的表达，并显著减轻慢性瘙痒的所有行为学体征。BB-SAP减少脊髓背角GRPR的表达，并显着减弱hyperknesis，对自发性抓挠或变应性没有影响。为了研究NK 1 R表达的脊髓神经元是否在上行体感通路中投射，我们进行了双标记研究。将荧光金（FG）逆行示踪剂注入躯体感觉丘脑或臂旁外侧核。在上颈（C1-2）脊髓，FG逆行标记的神经元大多位于背角浅层的背内侧。在FG标记的脊髓神经元中，89-94%为NK 1 R双标记。这些结果表明，NK 1 R表达脊髓神经元在慢性瘙痒症状的表达中起主要作用，并引起上升的体感投射。表达GRPR的脊髓神经元有助于运动机能亢进，但不会导致运动异常或持续性瘙痒。表达NK 1 R的脊髓神经元是治疗慢性瘙痒的潜在靶点。
We investigated roles for spinal neurons expressing the neurokinin-1 receptor (NK1R) and/or gastrin releasing peptide receptor (GRPR) in a mouse model of ovalbumin (OVA)-induced chronic atopic dermatitis (AD). Mice receiving repeated topical application of OVA exhibited atopic-like skin lesions and behavioral signs of chronic itch including spontaneous scratching, touch-evoked scratching (alloknesis), and enhancement of chloroquine-evoked scratching (hyperknesis). Substance P-saporin (SP-SAP) and bombesin-saporin (BB-SAP) were intrathecally injected into OVA-sensitized mice to neurotoxically ablate NK1R- or GRPR-expressing spinal neurons, respectively. SP-SAP diminished the expression of NK1R in the superficial spinal dorsal horn, and significantly attenuated all behavioral signs of chronic itch. BB-SAP reduced the spinal dorsal horn expression of GRPR and significantly attenuated hyperknesis, with no effect on spontaneous scratching or alloknesis. To investigate whether NK1R-expressing spinal neurons project in ascending somatosensory pathways, we performed a double-label study. The retrograde tracer, Fluorogold (FG), was injected into either the somatosensory thalamus or lateral parabrachial nucleus. In the upper cervical (C1-2) spinal cord, most neurons retrogradely labeled with FG were located in the dorsomedial aspect of the superficial dorsal horn. Of FG-labeled spinal neurons, 89-94% were double-labeled for NK1R. These results indicate that NK1R-expressing spinal neurons play a major role in the expression of symptoms of chronic itch, and give rise to ascending somatosensory projections. GRPR-expressing spinal neurons contribute to hyperknesis but not alloknesis or ongoing itch. NK1R-expressing spinal neurons represent a potential target to treat chronic itch.
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影响因子：
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