Dynorphin acts as a neuromodulator to inhibit itch in the dorsal horn of the spinal cord.
Dynorphin acts as a neuromodulator to inhibit itch in the dorsal horn of the spinal cord.
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DOI：
10.1016/j.neuron.2014.02.046
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发表时间：
2014-05-07
期刊：
影响因子：
16.2
通讯作者：
Ross SE
中科院分区：
文献类型：
--
作者：
Kardon AP;Polgár E;Hachisuka J;Snyder LM;Cameron D;Savage S;Cai X;Karnup S;Fan CR;Hemenway GM;Bernard CS;Schwartz ES;Nagase H;Schwarzer C;Watanabe M;Furuta T;Kaneko T;Koerber HR;Todd AJ;Ross SE
月经和其他反刺激缓解瘙痒，导致持续数分钟至数小时的抗瘙痒状态。然而，这种效应的神经基础尚不清楚，潜在的神经调节机制也不清楚。先前的研究表明，缺乏特定脊髓抑制性中间神经元（B5-I神经元）的Bhlhb 5 −/−小鼠会出现病理性瘙痒。在这里，我们表征B5-I神经元，并表明它们属于一个神经化学上不同的子集。我们提供了B5-I神经元抑制瘙痒的因果证据，并表明从B5-I神经元释放的强啡肽是瘙痒的关键神经调节剂。最后，我们表明，B5-I神经元受薄荷醇，辣椒素，芥子油反应的感觉神经元和薄荷醇抑制瘙痒所需的。这些发现为化学反刺激抑制瘙痒提供了细胞基础，并表明κ阿片类药物可能是病理性瘙痒的广泛有效的治疗方法。脊髓B5-I中间神经元的功能是抑制瘙痒B5-I神经元释放卡帕阿片强啡肽卡帕阿片信号双向调节脊髓内的瘙痒脊髓B5-I中间神经元介导薄荷醇对瘙痒的抑制Kardon等人。鉴定起抑制瘙痒作用的脊髓中间神经元群。从这些神经元释放κ阿片强啡肽介导化学反刺激物如薄荷醇对瘙痒的抑制，表明κ阿片类药物可能是病理性瘙痒的广泛有效的治疗方法。
Menthol and other counterstimuli relieve itch, resulting in an antipruritic state that persists for minutes to hours. However, the neural basis for this effect is unclear, and the underlying neuromodulatory mechanisms are unknown. Previous studies revealed that Bhlhb5−/− mice, which lack a specific population of spinal inhibitory interneurons (B5-I neurons), develop pathological itch. Here we characterize B5-I neurons and show that they belong to a neurochemically distinct subset. We provide cause-and-effect evidence that B5-I neurons inhibit itch and show that dynorphin, which is released from B5-I neurons, is a key neuromodulator of pruritus. Finally, we show that B5-I neurons are innervated by menthol-, capsaicin-, and mustard oil-responsive sensory neurons and are required for the inhibition of itch by menthol. These findings provide a cellular basis for the inhibition of itch by chemical counterstimuli and suggest that kappa opioids may be a broadly effective therapy for pathological itch. Spinal B5-I interneurons function to inhibit itch B5-I neurons release the kappa opioid dynorphin Kappa opioid signaling bidirectionally modulates itch within the spinal cord Spinal B5-I interneurons mediate the inhibition of itch by menthol Kardon et al. identify a population of spinal interneurons that function to inhibit itch. Release of the kappa opioid dynorphin from these neurons mediates the inhibition of itch by chemical counterstimuli such as menthol, suggesting that kappa opioids may be a broadly effective therapy for pathological itch.
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