Cross-sensitization of histamine-independent itch in mouse primary sensory neurons.

Cross-sensitization of histamine-independent itch in mouse primary sensory neurons.
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DOI:
10.1016/j.neuroscience.2012.09.019
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发表时间:
2012-12-13
期刊:
影响因子:
3.3
通讯作者:
Carstens, E.
Carstens, E.
中科院分区:
医学3区
文献类型:
--
作者:
Akiyama, T.;Tominaga, M.;Davoodi, A.;Nagamine, M.;Blansit, K.;Horwitz, A.;Carstens, M. I.;Carstens, E.

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瘙痒原及其前体的过度表达可能有助于组胺依赖和非依赖的瘙痒信号通路在慢性瘙痒中的敏化。目前,我们研究了不同瘙痒原引起的抓挠行为的自身和交叉敏感化,以及它们对初级感觉神经元的影响。MRgprC11激动剂BAM8-22对蛋白水解酶激活受体-2(PAR-2)激动剂SLIGRL引起的抓挠表现出自身和相互的交叉敏化作用。MRGPRA3激动剂氯喹单向交叉敏化BAM8-22引起划痕。组胺单向交叉敏化氯喹和BAM8-22引起的抓挠。SLIGRL单向交叉敏化氯喹引起的划痕。背根神经节(DRG)细胞对不同组合的瘙痒原和变应原有反应。氯喹、BAM8-22和组胺都不影响DRG细胞对随后应用的瘙痒原的反应,这意味着它们的行为自敏和交叉敏化效应是间接介导的。SLIGRL单侧交叉增敏DRG细胞对氯喹和BAM8-22的反应,与行为学数据一致。这些结果表明,组胺非依赖性瘙痒信号通路的单向交叉敏化可能通过PAR-2发生在外周部位。在瘙痒感觉神经末梢表达的PAR-2是减少与慢性瘙痒相关的敏感化的潜在靶点。
Overexpression of pruritogens and their precursors may contribute to the sensitization of histamine-dependent and –independent itch-signaling pathways in chronic itch. We presently investigated self- and cross-sensitization of scratching behavior elicited by various pruritogens, and their effects on primary sensory neurons. The MrgprC11 agonist BAM8–22 exhibited self- and reciprocal cross-sensitization of scratching evoked by the protease-activated receptor-2 (PAR-2) agonist SLIGRL. The MrgprA3 agonist chloroquine unidirectionally cross-sensitized BAM8–22-evoked scratching. Histamine unidirectionally cross-sensitized scratching evoked by chloroquine and BAM8–22. SLIGRL unidirectionally cross-sensitized scratching evoked by chloroquine. Dorsal root ganglion (DRG) cells responded to various combinations of pruritogens and algogens. Neither chloroquine, BAM8–22 nor histamine had any effect on responses of DRG cell responses to subsequently applied pruritogens, implying that their behavioral self- and cross-sensitization effects are mediated indirectly. SLIGRL unilaterally cross-sensitized responses of DRG cells to chloroquine and BAM8–22, consistent with the behavioral data. These results indicate that unidirectional cross-sensitization of histamine-independent itch-signaling pathways might occur at a peripheral site through PAR-2. PAR-2 expressed in pruriceptive nerve endings is a potential target to reduce sensitization associated with chronic itch.
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