University of California, Davis, Department of Neurobiology, Physiology & Behavior, 1 Shields Avenue, Davis, CA 95616, USA.
Neuroscience. 2012 Dec 13;226:305-12. doi: 10.1016/j.neuroscience.2012.09.019. Epub 2012 Sep 19.
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.
变应原及其前体的过度表达可能导致慢性瘙痒中组胺依赖性和非依赖性瘙痒信号通路的致敏。我们目前研究了各种瘙痒原引起的搔抓行为的自身和交叉致敏作用，以及它们对初级感觉神经元的影响。MrgprC11 激动剂 BAM8-22 表现出蛋白酶激活受体-2 (PAR-2) 激动剂 SLIGRL 引起的搔抓的自身和相互交叉致敏作用。MrgprA3 激动剂氯喹单向交叉致敏 BAM8-22 诱导的搔抓。组胺单向交叉致敏氯喹和 BAM8-22 诱导的搔抓。SLIGRL 单向交叉致敏氯喹诱导的搔抓。背根神经节 (DRG) 细胞对各种瘙痒原和致痛原的组合有反应。氯喹、BAM8-22 或组胺对随后应用的瘙痒原引起的 DRG 细胞反应均无影响，这表明它们的行为自身和交叉致敏作用是间接介导的。SLIGRL 单侧交叉致敏 DRG 细胞对氯喹和 BAM8-22 的反应，与行为数据一致。这些结果表明，通过 PAR-2，可能在周围部位发生非组胺依赖性瘙痒信号通路的单向交叉致敏。在瘙痒性神经末梢表达的 PAR-2 是减少与慢性瘙痒相关的致敏作用的潜在靶点。
