Estrogens influence female itch sensitivity via the spinal gastrin-releasing peptide receptor neurons.
Estrogens influence female itch sensitivity via the spinal gastrin-releasing peptide receptor neurons.
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DOI：
10.1073/pnas.2103536118
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发表时间：
2021-08-03
影响因子：
11.1
通讯作者：
Sakamoto H
中科院分区：
文献类型：
--
作者：
Takanami K;Uta D;Matsuda KI;Kawata M;Carstens E;Sakamoto T;Sakamoto H
许多妇女在怀孕期间表现出瘙痒的急剧增加，但其潜在机制尚不清楚。在这里，我们证明了雌性类固醇激素雌二醇，而不是孕酮，增强了由组胺引起的雌性大鼠瘙痒相关的抓挠行为，组胺是人类典型的瘙痒介质。这与脊髓背角神经元的一个子集的组胺诱发的活性增强有关，该神经元表达神经肽受体，胃泌素释放肽受体（GRPR），该受体先前被证明参与脊髓对瘙痒的处理。这些发现可能解释了为什么瘙痒感觉随雌激素水平而变化，并为通过靶向GRPR治疗女性组胺相关瘙痒疾病提供了基础。躯体感觉敏感性存在性别差异。循环中的雌激素似乎有一种致痛效应，这解释了为什么女性比男性对疼痛更敏感。虽然瘙痒症状在许多妇女怀孕期间发展，但女性特异性瘙痒的潜在机制尚不清楚。在这里，我们证明，雌二醇，而不是孕酮，增强组胺诱发的抓挠行为指示瘙痒的雌性大鼠。雌二醇增加了脊髓瘙痒介质胃泌素释放肽（GRP）的表达，并增加了脊髓背角表达GRP受体（GRPR）的瘙痒处理神经元的组胺诱发活性。鞘内注射GRPR阻滞剂可抑制雌二醇引起的瘙痒行为增强。在体电生理分析表明，雌二醇增加了组胺诱发的放电频率，延长了雌性大鼠脊髓GRP敏感神经元的反应。另一方面，雌二醇不影响伤害性热痛阈值和触觉敏感性降低，表明雌二醇分别影响瘙痒、疼痛和触觉模式。因此，雌激素通过脊髓GRP/GRPR系统选择性地增强女性组胺诱发的瘙痒。这可能解释了为什么瘙痒感觉随雌激素水平而变化，并为通过靶向GRPR治疗女性瘙痒提供了基础。
Many women exhibit a dramatic increase in itch during pregnancy, but the underlying mechanism is unknown. Here, we demonstrate that the female sex steroid hormone estradiol, but not progesterone, enhances itch-related scratching behavior in female rats elicited by histamine, the prototypical itch mediator in humans. This is associated with an enhancement in histamine-evoked activity of a subset of spinal dorsal horn neurons that express a neuropeptide receptor, gastrin-releasing peptide receptor (GRPR), that was previously shown to be involved in spinal cord processing of itch. These findings may account for why itch sensation varies with estrogen levels and provide a basis for treating histamine-related itch diseases in females by targeting GRPR. There are sex differences in somatosensory sensitivity. Circulating estrogens appear to have a pronociceptive effect that explains why females are reported to be more sensitive to pain than males. Although itch symptoms develop during pregnancy in many women, the underlying mechanism of female-specific pruritus is unknown. Here, we demonstrate that estradiol, but not progesterone, enhances histamine-evoked scratching behavior indicative of itch in female rats. Estradiol increased the expression of the spinal itch mediator, gastrin-releasing peptide (GRP), and increased the histamine-evoked activity of itch-processing neurons that express the GRP receptor (GRPR) in the spinal dorsal horn. The enhancement of itch behavior by estradiol was suppressed by intrathecal administration of a GRPR blocker. In vivo electrophysiological analysis showed that estradiol increased the histamine-evoked firing frequency and prolonged the response of spinal GRP-sensitive neurons in female rats. On the other hand, estradiol did not affect the threshold of noxious thermal pain and decreased touch sensitivity, indicating that estradiol separately affects itch, pain, and touch modalities. Thus, estrogens selectively enhance histamine-evoked itch in females via the spinal GRP/GRPR system. This may explain why itch sensation varies with estrogen levels and provides a basis for treating itch in females by targeting GRPR.
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影响因子：
3.6
作者：
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