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.

体感敏感性存在性别差异。循环雌激素似乎具有促痛作用，这解释了为什么据报道女性比男性对疼痛更敏感。尽管许多女性在怀孕期间会出现瘙痒症状，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，但不是黄体酮，增强了组胺诱发的搔抓行为，表明雌性大鼠瘙痒。雌二醇增加了脊髓瘙痒介质胃泌素释放肽 (GRP) 的表达，并增加了表达脊髓背角 GRP 受体 (GRPR) 的瘙痒处理神经元的组胺诱发活性。鞘内施用 GRPR 阻滞剂可抑制雌二醇对瘙痒行为的增强作用。体内电生理分析表明，雌二醇增加了组胺诱发的放电频率，并延长了雌性大鼠脊髓 GRP 敏感神经元的反应。另一方面，雌二醇不影响有害热痛的阈值和降低触觉敏感性，表明雌二醇分别影响瘙痒、疼痛和触觉方式。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。这可以解释为什么瘙痒感会随着雌激素水平的变化而变化，并为通过靶向 GRPR 治疗女性瘙痒提供了基础。表明雌二醇分别影响瘙痒、疼痛和触摸方式。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。这可以解释为什么瘙痒感会随着雌激素水平的变化而变化，并为通过靶向 GRPR 治疗女性瘙痒提供了基础。表明雌二醇分别影响瘙痒、疼痛和触摸方式。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。这可以解释为什么瘙痒感会随着雌激素水平的变化而变化，并为通过靶向 GRPR 治疗女性瘙痒提供了基础。