Scratching Behavior and Fos Expression in Superficial Dorsal Horn Elicited by Protease-Activated Receptor Agonists and Other Itch Mediators in Mice
Scratching Behavior and Fos Expression in Superficial Dorsal Horn Elicited by Protease-Activated Receptor Agonists and Other Itch Mediators in Mice
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DOI：
10.1124/jpet.109.152256
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发表时间：
2009-06-01
影响因子：
3.5
通讯作者：
Carstens, E.
中科院分区：
文献类型：
--
作者：
Akiyama, Tasuku;Merrill, Austin W.;Carstens, E.
蛋白酶激活受体（PAR）-2和PAR-4与非组胺性瘙痒有关。我们研究了皮内注射PAR-2和PAR-4激动剂、血清素（5-羟色胺，5-HT）和组胺在ICR小鼠中引起的瘙痒相关抓挠的剂量依赖性、快速耐受性和交叉快速耐受性，以及PAR-2激动剂诱发抓挠的μ阿片调节。每种药物引起抓挠发作的剂量相关性增加。由PAR-4激动剂和组胺引起的痉挛均表现出显著的快速耐受性，但彼此之间没有交叉快速耐受性。由5-HT引起的抓挠没有表现出显著的快速耐受性，但对由PAR-2和PAR-4激动剂和组胺引起的抓挠表现出显著的交叉快速耐受性。纳洛酮和高剂量吗啡（10 mg/kg）减弱PAR-2激动剂诱发的抓挠，而低剂量吗啡（1 mg/kg）则无影响。高剂量的吗啡也显著增加了盘旋行为，这可能干扰了抓挠。PAR-2激动剂和5-HT产生重叠分布的Fos样免疫反应在浅背角。这些结果表明，PAR-2和PAR-4激动剂，组胺和5-HT引起瘙痒相关的抓挠和激活浅背角神经元，可能参与抓挠反射和上行瘙痒信号通路。
Protease-activated receptor (PAR)-2 and PAR-4 are implicated in nonhistaminergic itch. We investigated dose dependence, tachyphylaxis, and cross-tachyphylaxis of itch-associated scratching elicited by intradermal injections of PAR-2 and PAR-4 agonists, serotonin (5-hydroxytryptamine, 5-HT), and histamine in ICR mice, as well as mu-opioid modulation of PAR-2 agonist-evoked scratching. Each agent elicited dose-related increases in scratch bouts. Scratching elicited by the PAR-4 agonist and histamine both exhibited significant tachyphylaxis but no cross-tachyphylaxis with each other. Scratching evoked by 5-HT did not exhibit significant tachyphylaxis but did exhibit significant cross-tachyphylaxis to scratching evoked by the PAR-2 and PAR-4 agonists and histamine. Naltrexone and high-dose morphine (10 mg/kg) attenuated PAR-2 agonist-evoked scratching, whereas lower dose morphine (1 mg/kg) had no effect. High-dose morphine also significantly increased circling behavior, which may have interfered with scratching. The PAR-2 agonist and 5-HT produced overlapping distributions of Fos-like immunoreactivity in the superficial dorsal horn. These results indicate that PAR-2 and PAR-4 agonists, histamine, and 5-HT elicit itch-related scratching and activate superficial dorsal horn neurons that may participate in scratch reflex and ascending itch signaling pathways.