Enhanced responses of lumbar superficial dorsal horn neurons to intradermal PAR-2 agonist but not histamine in a mouse hindpaw dry skin itch model
Enhanced responses of lumbar superficial dorsal horn neurons to intradermal PAR-2 agonist but not histamine in a mouse hindpaw dry skin itch model
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DOI：
10.1152/jn.01124.2010
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发表时间：
2011-06-01
影响因子：
2.5
通讯作者：
Carstens, E.
中科院分区：
文献类型：
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作者：
Akiyama, Tasuku;Carstens, Mirela Iodi;Carstens, E.
Akiyama T，Carstens MI，Carstens E.在小鼠后爪干燥皮肤瘙痒模型中，腰浅背角神经元对皮内PAR-2激动剂而非组胺的反应增强。J Neurophysiol 105：2811-2817，2011.首次发表于2011年3月23日; doi：10.1152/jn.01124.2010.-慢性瘙痒是许多皮肤病和全身性疾病的症状。关于与慢性瘙痒相关的瘙痒信号神经通路的病理生理学改变知之甚少。我们使用小鼠后爪慢性皮肤干燥瘙痒模型来研究假定瘙痒信号神经元的特性。后爪干燥皮肤处理同侧的腰浅背角中的神经元表现出高水平的自发活动，该自发活动通过抓挠足底表面而被抑制。皮内注射蛋白酶激活受体PAR-2或组胺激动剂后，大多数自发活动单位的放电率进一步增加。绝大多数过敏原反应单位也对辣椒素和异硫氰酸烯丙酯有反应。对于神经元同侧干燥皮肤治疗，PAR-2激动剂引起的反应，但不是组胺或机械刺激，显着更大的神经元同侧的车辆（水）治疗或神经元记录在幼稚（未处理）小鼠。自发活动可能是持续瘙痒的信号，而增强的PAR-2激动剂诱发的反应可能是运动过度（瘙痒增强）的基础，这两者都是许多慢性瘙痒病症的症状。PAR-2激动剂引起的神经元反应的增强，而不是组胺或机械刺激，这意味着干燥的皮肤条件选择性致敏PAR-2激动剂敏感的初级传入神经元受体。
Akiyama T, Carstens MI, Carstens E. Enhanced responses of lumbar superficial dorsal horn neurons to intradermal PAR-2 agonist but not histamine in a mouse hindpaw dry skin itch model. J Neurophysiol 105: 2811-2817, 2011. First published March 23, 2011; doi:10.1152/jn.01124.2010.-Chronic itch is symptomatic of many skin conditions and systemic diseases. Little is known about pathophysiological alterations in itch-signaling neural pathways associated with chronic itch. We used a mouse model of hindpaw chronic dry skin itch to investigate properties of presumptive itch-signaling neurons. Neurons in the lumbar superficial dorsal horn ipsilateral to hindpaw dry skin treatment exhibited a high level of spontaneous activity that was inhibited by scratching the plantar surface. Most spontaneously active units exhibited further increases in firing rate following intradermal injection of an agonist of the protease-activated receptor PAR-2, or histamine. The large majority of pruritogen-responsive units also responded to capsaicin and allyl isothiocyanate. For neurons ipsilateral to dry skin treatment, responses elicited by the PAR-2 agonist, but not histamine or mechanical stimuli, were significantly larger compared with neurons ipsilateral to vehicle (water) treatment or neurons recorded in naive (untreated) mice. The spontaneous activity may signal ongoing itch, while enhanced PAR-2 agonist-evoked responses may underlie hyperknesis (enhanced itch), both of which are symptomatic of many chronic itch conditions. The enhancement of neuronal responses evoked by the PAR-2 agonist, but not by histamine or mechanical stimuli, implies that the dry skin condition selectively sensitized PAR-2 agonist-sensitive primary afferent pruriceptors.