Bulleyaconitine A Inhibits Itch and Itch Sensitization Induced by Histamine and Chloroquine

Bulleyaconitine A Inhibits Itch and Itch Sensitization Induced by Histamine and Chloroquine
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Bulleyaconitine A 抑制组胺和氯喹引起的瘙痒和瘙痒致敏

DOI:
10.1016/j.neuroscience.2019.12.048
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发表时间:
2020-01
期刊:
影响因子:
3.3
通讯作者:
Liu Xian-Guo
Liu Xian-Guo
中科院分区:
医学3区
文献类型:
--
作者:
Huang Zhuo;Zhou Xin;Zhang Jun;Mai Chun-Lin;Mai Jie-Zhen;Liu Chong;Zhang Hui;Liu Xian-Guo

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瘙痒(瘙痒症),特别是与疾病状况相关的慢性瘙痒,显著损害患者的生活质量。目前,这种令人厌恶的经历背后的机制仍不清楚,瘙痒的有效治疗在很大程度上尚未得到满足。在此,我们报告了在中国已被用于治疗慢性疼痛30年的草乌甲素(BLA)灌胃给药,抑制由皮内注射组胺和氯喹引起的小鼠和大鼠的瘙痒样行为,并呈剂量依赖性。我们发现,一个单一的应用程序的消炎药在皮肤区域的腓肠神经支配诱导长时程增强(LTP)的C-纤维场电位诱发的刺激相同的神经在脊髓背角的大鼠。脊髓应用BLA或胃泌素释放肽受体(GRPR)拮抗剂(PD 176252)可显著逆转脊髓LTP。PD 176252的作用被BLA完全阻断,而BLA的作用仅被PD 176252部分阻断。在颈后重复注射组胺或氯喹(每天一次,共4天)可逐渐增强抓挠行为,且瘙痒致敏作用在停止注射后至少持续1周。行为学改变伴随着背角C纤维突触传递的增强。灌胃BLA可明显减弱瘙痒敏感性和突触增强作用。总之,BLA可有效抑制组胺依赖性和组胺非依赖性瘙痒,这些作用的潜在机制涉及但不限于抑制脊髓背角中的胃泌素释放肽(GRP)-GRPR信号传导。
Itch (pruritus), specifically chronic itch associated with disease conditions, significantly impairs the patient’s quality of life. At present, the mechanisms underlying this aversive experience are still unclear, and the effective treatment of itch is largely unmet. Here, we report that intragastrical administration of bulleyaconitine A (BLA), which has been used for treating chronic pain for 30 years in China, inhibited itch-like behaviors induced by intradermal injection of histamine and chloroquine in mice and rats, dose-dependently. We found that a single application of the pruritic agents at the skin region innervated by the sural nerve induced long-term potentiation (LTP) of C-fiber field potentials evoked by the stimulation of the same nerve in the spinal dorsal horn of rats. The spinal LTP was remarkably reversed by the spinal application of either BLA or gastrin-releasing peptide receptor (GRPR) antagonist (PD176252). The effect of PD176252 was completely occluded by BLA, while the effect of BLA was only partially occluded by PD176252. Repetitive injection (daily, for four days) of either histamine or chloroquine in the back of the neck enhanced scratching behaviors progressively, and the itch sensitization persisted for at least one week after the discontinuation of the injections. The behavioral change was accompanied with the potentiation of C-fiber synaptic transmission in the dorsal horn. Both the itch sensitization and synaptic potentiation were substantially attenuated by intragastrical BLA. Together, BLA was effective in inhibiting histamine-dependent and histamine-independent itches, and the mechanisms underlying these effects were involved but not limited to the inhibition of gastrin-releasing peptide (GRP)–GRPR signaling in the spinal dorsal horn.
DOI: --
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发表时间: 2011-01-01
影响因子: 3.6
作者:
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DOI: 10.1126/science.1127233
发表时间: 2006-06-16
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DOI: --
发表时间: 2011
期刊: --
影响因子: --
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通讯作者: --