Estrogen alleviates neuropathic pain induced after spinal cord injury by inhibiting microglia and astrocyte activation
Estrogen alleviates neuropathic pain induced after spinal cord injury by inhibiting microglia and astrocyte activation
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DOI：
10.1016/j.bbadis.2018.04.006
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发表时间：
2018-07-01
影响因子：
6.2
通讯作者：
Yune, Tae Young
中科院分区：
文献类型：
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作者：
Lee, Jee Youn;Choi, Hae Young;Yune, Tae Young
大约80%的SCI患者会出现脊髓损伤(SCI)后的神经病理性疼痛，并且没有有效的治疗药物来缓解SCI引起的神经病理性疼痛。在这里，我们研究了雌激素对 SCI 诱发的神经病理性疼痛的影响及其对神经炎症的影响作为潜在机制。神经性疼痛发生在SCI后的晚期，通过静脉注射给SCI后出现神经性疼痛的大鼠单剂量17β-雌二醇(100、300μg/kg)。结果，与赋形剂对照相比，17β-雌二醇显着降低了机械性异常性疼痛和热痛觉过敏。 L4-5 背角 I 层和 II 层中的小胶质细胞和星形胶质细胞的活化也受到 17 β-雌二醇的抑制。此外，17β-雌二醇显着降低了已知在小胶质细胞中激活的p-p38MAPK和p-ERK以及已知在星形胶质细胞中激活的p-JNK的水平。此外，17β-雌二醇治疗组中炎症介质（例如 Il-1 beta 6、Il-6、iNos 和 Cox-2）的 mRNA 表达比媒介物治疗组更加减弱。特别是，我们发现17β-雌二醇的镇痛作用是通过雌激素受体介导的，雌激素受体在背角神经元中表达。这些结果表明，17β-雌二醇可能通过抑制炎症后的小胶质细胞和星形胶质细胞活化来减轻 SCI 引起的神经性疼痛。
Neuropathic pain after spinal cord injury (SCI) is developed in about 80% of SCI patients and there is no efficient therapeutic drug to alleviate SCI-induced neuropathic pain. Here we examined the effect of estrogen on SCI-induced neuropathic pain at below-level and its effect on neuroinflammation as underlying mechanisms. Neuropathic pain is developed at late phase after SCI and a single dose of 17 beta-estradiol (100, 300 mu g/kg) were administered to rats with neuropathic pain after SCI through intravenous injection. As results, both mechanical allodynia and thermal hyperalgesia were significantly reduced by 17 beta-estradiol compared to vehicle control. Both microglia and astrocyte activation in the lamina I and II of L4-5 dorsal horn was also inhibited by 17 beta-estradiol. In addition, the levels of p-p38MAPK and p-ERK known to be activated in microglia and p-JNK known to be activated in astrocyte were significantly decreased by 17 beta-estradiol. Furthermore, the mRNA expression of inflammatory mediators such as Il-1 beta 6, Il-6, iNos, and Cox-2 was more attenuated in 17 beta-estradiol-treated group than in vehicle-treated group. Particularly, we found that the analgesic effect by 17 beta-estradiol was mediated via estrogen receptors, which are expressed in dorsal horn neurons. These results suggest that 17 beta-estradiol may attenuate SCI-induced neuropathic pain by inhibiting microglia and astrocyte activation followed inflammation.