Neonatal Injury Modulates Incisional Pain Sensitivity in Adulthood: An Animal Study
Neonatal Injury Modulates Incisional Pain Sensitivity in Adulthood: An Animal Study
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DOI：
10.1016/j.neuroscience.2023.03.018
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发表时间：
2023-03-30
期刊：
影响因子：
3.3
通讯作者：
Shinoda，Masamichi
中科院分区：
文献类型：
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作者：
Soma，Kumi;Hitomi，Suzuro;Shinoda，Masamichi
新生儿疼痛经历包括创伤性损伤对伤害性回路的发育产生负面影响，导致成人持续性疼痛超敏反应。然而，详细的机制还没有得到很好的理解。为探讨新生大鼠面部皮肤切口痛超敏反应的发病机制，本研究检测了190只新生大鼠面部皮肤切口痛超敏反应中三叉神经节内电压门控钠通道（Nav）1.8和C-C趋化因子配体2（CCL 2）/C-C趋化因子受体2（CCR 2）信号通路的变化。分别于生后第4天和第7周切取须垫皮肤（切口-切口组）。与无新生儿切口组（假切口组）相比，切口-切口组胡须垫皮肤的机械超敏反应增强。与假手术组相比，再次手术后第14天，切口组TG内Nav1.8免疫反应阳性神经元数量及TG内巨噬细胞和卫星胶质细胞中CCL 2的表达量均增加。在切口-切口组中，切口区域中Nav1.8和TG中CCR 2的阻断抑制了机械超敏反应的增强。在假手术-假手术组、切口-假手术组和假手术-切口组中，将CCL 2施用到TG中增强了机械超敏性。我们的研究结果表明，新生儿面部损伤加速了TG神经元的过度兴奋性与Nav1.8过度表达通过CCL 2信号，导致在成年期口面部切口疼痛超敏反应的增强。
Neonatal pain experiences including traumatic injury influences negatively on development of nociceptive circuit developments, resulting in persistent pain hypersensitivity in adults. However, the detailed mechanism is not yet well understood. In the present study, to clarify the pathogenesis of orofacial pain hypersensitivity associated with neonatal injury, the involvement of the voltage-gated sodium channel (Nav) 1.8 and the C-C chemokine ligand 2 (CCL2)/C-C chemokine receptor 2 (CCR2) signaling in the trigeminal ganglion (TG) in facial skin incisional pain hypersensitivity was examined in 190 neonatal facial-injured and sham male rats. The whisker pad skin was incised on postnatal day 4 and week 7 (Incision–Incision group). Compared to the group without neonatal incision (Sham–Incision group), mechanical hypersensitivity in the whisker pad skin was enhanced in Incision-Incision group. The number of Nav1.8-immunoreactive TG neurons and the amount of CCL2 expressed in the macrophages and satellite glial cells in the TG were increased on day 14 after re-incision in the Incision–Incision group, compared with Sham-Incision group. Blockages of Nav1.8 in the incised region and CCR2 in the TG suppressed the enhancement of mechanical hypersensitivity in the Incision–Incision group. Administration of CCL2 into the TG enhanced mechanical hypersensitivity in the Sham-Sham, Incision-Sham and Sham–Incision group. Our results suggest that neonatal facial injury accelerates the TG neuronal hyperexcitability following orofacial skin injury in adult in association with Nav1.8 overexpression via CCL2 signaling, resulting in the enhancement of orofacial incisional pain hypersensitivity in the adulthood.