Jayasena Channa N, Comninos Alexander N, Stefanopoulou Evgenia, Buckley Adam, Narayanaswamy Shakunthala, Izzi-Engbeaya Chioma, Abbara Ali, Ratnasabapathy Risheka, Mogford Julianne, Ng Noel, Sarang Zubair, Ghatei Mohammad A, Bloom Stephen R, Hunter Myra S, Dhillo Waljit S
Section of Investigative Medicine, Imperial College London, Hammersmith Hospital, London, UK.
Department of Psychology, Institute of Psychiatry, King's College London, Guy's Hospital, London, UK.
Sci Rep. 2015 Feb 16;5:8466. doi: 10.1038/srep08466.
Neurokinin B (NKB) is a hypothalamic neuropeptide binding preferentially to the neurokinin 3 receptor. Expression of the gene encoding NKB is elevated in postmenopausal women. Furthermore, rodent studies suggest that NKB signalling may mediate menopausal hot flushes. However, the effects of NKB administration on hot flushes have not been investigated in humans. To address this, we performed a randomised, double-blinded, placebo-controlled, 2-way cross-over study. Ten healthy women were admitted to a temperature and humidity-controlled research unit. Participants received 30 minute intravenous infusions of NKB and vehicle in random order. Symptoms, heart rate, blood pressure, sweating and skin temperature were compared between NKB and vehicle in a double-blinded manner. Eight of ten participants experienced flushing during NKB infusion with none experiencing flushing during vehicle infusion (P = 0.0007). Significant elevations in heart rate (P = 0.0106 vs. pre-symptoms), and skin temperature measured using skin probe (P = 0.0258 vs. pre-symptoms) and thermal imaging (P = 0.0491 vs. pre-symptoms) characteristic of menopausal flushing were observed during hot flush episodes. Our findings provide evidence that NKB administration can cause hot flushes in women. Further studies are required to determine if pharmacological blockade of NKB signalling could inhibit hot flushes during the menopause and during treatment for sex-steroid dependent cancers.
神经激肽B（NKB）是一种下丘脑神经肽，它优先与神经激肽3受体结合。编码NKB的基因在绝经后女性中的表达会升高。此外，啮齿动物研究表明，NKB信号传导可能介导绝经后潮热。然而，NKB给药对潮热的影响尚未在人体中进行研究。为了解决这个问题，我们进行了一项随机、双盲、安慰剂对照的双向交叉研究。10名健康女性被纳入一个温度和湿度可控的研究单元。参与者以随机顺序接受30分钟的NKB静脉输注和载体输注。以双盲方式比较NKB输注和载体输注期间的症状、心率、血压、出汗和皮肤温度。10名参与者中有8名在输注NKB期间出现潮热，而在输注载体期间无人出现潮热（P = 0.0007）。在潮热发作期间，观察到心率（与症状前相比，P = 0.0106）、使用皮肤探头测量的皮肤温度（与症状前相比，P = 0.0258）和热成像（与症状前相比，P = 0.0491）出现绝经后潮热特有的显著升高。我们的研究结果提供了证据，证明NKB给药可导致女性潮热。需要进一步研究以确定NKB信号传导的药理学阻断是否可以在绝经期间以及在性类固醇依赖性癌症的治疗期间抑制潮热。
