Microglial activation in the trigeminal spinal subnucleus interpolaris/caudalis modulates orofacial incisional mechanical pain hypersensitivity associated with orofacial injury in infancy

Microglial activation in the trigeminal spinal subnucleus interpolaris/caudalis modulates orofacial incisional mechanical pain hypersensitivity associated with orofacial injury in infancy
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DOI:
10.2334/josnusd.20-0648
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发表时间:
2021-03-01
影响因子:
1.9
通讯作者:
Shinoda, Masamichi
Shinoda, Masamichi
中科院分区:
工程技术4区
文献类型:
--
作者:
Matsui, Tomoyuki;Hitomi, Suzuro;Shinoda, Masamichi

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目的:婴幼儿组织损伤导致成人感觉障碍。据报道,婴儿面部切口(IFI)在成年后由于三叉神经节神经元兴奋性的加速而引起机械超敏反应的增强。然而,IFI对三叉神经脊束核小胶质细胞的激活及其参与面部疼痛敏感性的影响尚不清楚。方法:在幼年和/或成年大鼠的左侧胡须垫上制作面部皮肤切口。对机械头部戒断阈值和三叉神经脊束核小胶质细胞激活情况进行分析。结果:IFI可明显加重和延长AFI所致的机械痛过敏反应。IFI可增加AFI后三叉神经脊束核Iba1免疫反应细胞的数量,提示IFI可促进AFI后小胶质细胞的过度激活。小胶质细胞激活抑制剂米诺环素可抑制面部创伤后三叉神经脊束核小胶质细胞的过度激活和面部机械痛过敏的加重。结论:婴幼儿面部创伤后三叉神经脊束核小胶质细胞过度激活,导致面部机械痛过敏时间延长。
Purpose: Infantile tissue injury induces sensory deficits in adulthood. Infantile facial incision (IFI) was reported to cause an enhancement of incision-induced mechanical hypersensitivity in adulthood due to acceleration of the trigeminal ganglion neuronal excitability. However, the effects of IFI on activation of microglia in the spinal trigeminal nucleus and its involvement in facial pain sensitivity is not well known.Methods: A facial skin incision was made in the left whisker pad in infant (IFI) and/or adult rats (AFI). Mechanical head withdrawal threshold and microglial activation in the trigeminal spinal nucleus were analyzed.Results: Mechanical pain hypersensitivity induced by AFI was significantly exacerbated and prolonged by IFI. The number of Iba1-immunoreactive cells in the trigeminal spinal nucleus following AFI was increased by IFI, suggesting that IFI facilitates microglial hyperactivation following AFI. Intraperitoneal administration of minocycline, a microglial activation inhibitor, suppressed the facial incision-induced microglial hyperactivation in the trigeminal spinal nucleus and the exacerbation of the facial mechanical pain hypersensitivity induced by IFI.Conclusion: These results suggest that facial trauma in infants causes hyperactivation of microglia in the trigeminal spinal nucleus following AFI, leading to the prolongation of the facial mechanical pain hypersensitivity.