Fu Kai, Qu Lintao, Shimada Steven G, Nie Hong, LaMotte Robert H
Department of Anesthesiology, Yale University School of Medicine, New Haven, CT 06520, USA; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong, China.
Department of Anesthesiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Neurosci Lett. 2014 Sep 5;579:190-4. doi: 10.1016/j.neulet.2014.03.062. Epub 2014 Apr 3.
Chemical pruritogens and algogens evoke primarily itch and pain, respectively, when administered to the skin of healthy human subjects. However, the dominant sensory quality elicited by an algesic chemical stimulus may change in patients with chronic itch where bradykinin, elicits itch in addition to pain. Here we tested whether normally pruritic and algesic chemicals evoked abnormal itch- or pain-like behaviors in the mouse after the development of contact hypersensitivity (CHS), an animal model of allergic contact dermatitis. Mice previously sensitized to a hapten (squaric acid dibutylester) applied to the abdomen, exhibited spontaneous itch-like scratching and pain-like wiping directed to the site on the cheek of the CHS elicited by a subsequent challenge with the same hapten. In comparison with responses of control mice, CHS mice exhibited a significant increase in the scratching evoked by bovine adrenal medulla 8-22, a peptide that elicits a histamine-independent itch, but did not alter the scratching to histamine. Bradykinin, an algogen that elicited only wiping in control mice, additionally evoked significant scratching in CHS mice. Thus, within an area of CHS, histamine-independent itch is enhanced and chemically evoked pain is accompanied by itch.
当将化学性致痒原和致痛原分别施用于健康人类受试者的皮肤时,它们主要分别引发瘙痒和疼痛。然而,在患有慢性瘙痒的患者中,痛觉化学刺激引发的主要感觉性质可能会发生变化,其中缓激肽除了引发疼痛外还会引发瘙痒。在这里,我们测试了在接触性超敏反应(CHS,一种过敏性接触性皮炎的动物模型)发生后,正常情况下引起瘙痒和疼痛的化学物质是否会在小鼠中引发异常的瘙痒样或疼痛样行为。先前对涂抹于腹部的半抗原(二丁基酒石酸)致敏的小鼠,在用相同半抗原进行后续激发后,会在CHS的脸颊部位表现出自发的瘙痒样抓挠和疼痛样擦拭行为。与对照小鼠的反应相比,CHS小鼠对牛肾上腺髓质8 - 22(一种引发非组胺依赖性瘙痒的肽)引发的抓挠显著增加,但对组胺的抓挠没有改变。缓激肽,一种在对照小鼠中仅引发擦拭行为的致痛原,在CHS小鼠中还额外引发了显著的抓挠。因此,在CHS区域内,非组胺依赖性瘙痒增强,化学性诱发的疼痛伴有瘙痒。