Zhang Li, Zhang Jiang-Tao, Huang Ya, Zhou Guo-Kun, Zhou Yan, Yang Jiang-Ping, Liu Tong
Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Department of Anesthesiology, The First People's Hospital of Kunshan Affiliated with Jiangsu University, Kunshan, China.
Ann Transl Med. 2022 Sep;10(18):972. doi: 10.21037/atm-22-3804.
Itch is a common symptom of skin diseases and significantly reduces patients' quality of life. Melatonin has anti-inflammatory and antioxidant effects. Our study examined the potential anti-itch effects of melatonin (N-acetyl-5-methoxytryptamine) in mice.
We detected the effects of melatonin and its receptors on acute and chronic itch by conducting itching behavioral experiments in male C57 mice. Reactive oxygen species (ROS) levels and calcium ion (Ca) mobilization during acute itching production were explored using flow cytometry and calcium imaging techniques. Melatonin expression in the serum of the chronic itch model mice was determined by enzyme-linked immunoassays. Hematoxylin and eosin staining show the effects of melatonin on skin thickness in a chronic itch model. Cytokine and chemokine levels were determined by quantitative polymerase chain reaction.
We discovered that compound 48/80 (C48/80)- and chloroquine (CQ)-induced scratching were significantly decreased by intraperitoneal (i.p), intradermal, and intrathecal administration of melatonin in a dose-dependent manner in mice, and the co-administration of melatonin receptor antagonists abolished the anti-itch effects of i.d melatonin. The incubation of melatonin significantly decreased the intracellular ROS levels induced by C48/80 and CQ in cultured ND7/23 cells from a mouse x rat hybridoma nerve as neuron. Melatonin inhibited intracellular Ca increases induced by CQ (but not C48/80) in cultured dorsal root ganglia (DRG) neurons. Melatonin (50 mg/kg i.p) attenuated imiquimod (IMQ)- or acetone and diethyl ether followed by acetone-ether-water (AEW)-induced chronic itch and epidermal hyperplasia in mice. Finally, melatonin treatment reduced the IMQ-induced expression of ST2 and interleukin-33 (IL-33) or the AEW-induced expression of interleukin 31 (IL-31) and interleukin 31 receptor A (IL-31 RA) in the mice.
Collectively, our results indicate that melatonin attenuates acute and chronic itch, possibly via melatonin receptors, and its antioxidant, and anti-inflammatory effects in mice.
瘙痒是皮肤病的常见症状，会显著降低患者的生活质量。褪黑素具有抗炎和抗氧化作用。我们的研究检测了褪黑素（N - 乙酰 - 5 - 甲氧基色胺）在小鼠中的潜在止痒作用。
我们通过在雄性C57小鼠中进行瘙痒行为实验，检测褪黑素及其受体对急性和慢性瘙痒的影响。使用流式细胞术和钙成像技术探索急性瘙痒产生过程中的活性氧（ROS）水平和钙离子（Ca）动员情况。通过酶联免疫测定法测定慢性瘙痒模型小鼠血清中的褪黑素表达。苏木精和伊红染色显示褪黑素对慢性瘙痒模型皮肤厚度的影响。通过定量聚合酶链反应测定细胞因子和趋化因子水平。
我们发现，在小鼠中，腹腔内（i.p）、皮内和鞘内给予褪黑素以剂量依赖的方式显著降低了化合物48/80（C48/80）和氯喹（CQ）诱导的抓挠行为，并且联合给予褪黑素受体拮抗剂消除了皮内注射褪黑素的止痒作用。褪黑素孵育显著降低了来自小鼠×大鼠杂交瘤神经作为神经元的培养ND7/23细胞中由C48/80和CQ诱导的细胞内ROS水平。褪黑素抑制了培养的背根神经节（DRG）神经元中由CQ（而非C48/80）诱导的细胞内Ca增加。褪黑素（50 mg/kg i.p）减轻了咪喹莫特（IMQ）或丙酮和乙醚随后是丙酮 - 乙醚 - 水（AEW）诱导的小鼠慢性瘙痒和表皮增生。最后，褪黑素治疗降低了小鼠中IMQ诱导的ST2和白细胞介素 - 33（IL - 33）的表达或AEW诱导的白细胞介素31（IL - 31）和白细胞介素31受体A（IL - 31 RA）的表达。
总体而言，我们的结果表明，褪黑素可能通过褪黑素受体及其抗氧化和抗炎作用减轻急性和慢性瘙痒。
