Estradiol modulates visceral hyperalgesia by increasing thoracolumbar spinal GluN2B subunit activity in female rats.
Estradiol modulates visceral hyperalgesia by increasing thoracolumbar spinal GluN2B subunit activity in female rats.
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DOI：
10.1111/nmo.12549
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发表时间：
2015-06
影响因子：
3.5
通讯作者：
Traub RJ
中科院分区：
文献类型：
--
作者：
Ji Y;Bai G;Cao DY;Traub RJ
我们以前报道过雌激素通过改变脊髓GluN 1亚基磷酸化/表达来调节脊髓NMDA受体对结直肠疼痛的处理。本研究的目的是探讨是否脊髓谷氨酸2B含有NMDA受体参与雌激素调节内脏痛加工。行为，分子和免疫细胞化学技术被用来确定脊髓GluN 2B的表达/磷酸化和功能48小时后，皮下注射雌二醇（E2）或车辆（红花油，藏红花油）在卵巢切除大鼠在不存在或存在的结肠炎症诱导芥子油。E2增加了内脏反应（VMR）的幅度，以结直肠扩张相比，在非炎症大鼠的藏红花油。鞘内注射GluN 2B亚基拮抗剂Ro 25-6981对非炎症E2或Saff油大鼠的VMR没有影响。结肠炎症在E2大鼠中诱导内脏痛觉过敏，但在Saff油大鼠中则不然。鞘内注射GluN 2B亚单位选择性拮抗剂可阻断E2大鼠内脏痛觉过敏。在炎症大鼠中，E2增加了胸腰椎（TL）中GluN 2B蛋白和基因的表达，但不增加腰骶（LS）和背侧脊髓中的GluN 2B蛋白和基因的表达。免疫细胞化学标记显示E2大鼠背角浅层GluN 2B亚基的表达显著增加。这些数据支持了雌激素通过增加NMDA受体活性来增加结肠炎症诱导的内脏痛觉过敏的脊髓加工的假设。具体地说，雌激素增加TL脊髓中含有NMDA受体的GluN 2B的活性是结肠炎症存在下内脏高敏感性的基础。
We previously reported estrogen modulates spinal NMDA receptor processing of colorectal pain through changes in spinal GluN1 subunit phosphorylation/expression. The purpose of the present study was to investigate whether spinal GluN2B containing NMDA receptors are involved in estrogen modulation of visceral pain processing. Behavioral, molecular and immunocytochemical techniques were used to determine spinal GluN2B expression/phosphorylation and function 48 hrs following subcutaneous injection of estradiol (E2) or vehicle (safflower oil, Saff oil) in ovariectomized rats in the absence or presence of colonic inflammation induced by mustard oil. E2 increased the magnitude of the visceromotor response (VMR) to colorectal distention compared to Saff oil in non-inflamed rats. Intrathecal injection of the GluN2B subunit antagonist, Ro 25-6981, had no effect on the VMR in non-inflamed E2 or Saff oil rats. Colonic inflammation induced visceral hyperalgesia in E2, but not Saff oil rats. Visceral hyperalgesia in E2 rats was blocked by intrathecal GluN2B subunit selective antagonists. In inflamed rats, E2 increased GluN2B protein and gene expression in the thoracolumbar (TL), but not lumbosacral (LS), dorsal spinal cord. Immunocytochemical labeling showed a significant increase of GluN2B subunit in the superficial dorsal horn of E2 rats compared to Saff oil rats. These data support the hypothesis that estrogen increases spinal processing of colonic inflammation-induced visceral hyperalgesia by increasing NMDA receptor activity. Specifically, an increase in the activity of GluN2B containing NMDA receptors in the TL spinal cord by estrogen underlies visceral hypersensitivity in the presence of colonic inflammation.
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大鼠瞬时和炎症性结直肠刺激的脊柱加工性别差异。
影响因子：
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作者：
Ji Y;Tang B;Cao DY;Wang G;Traub RJ
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