Age-related Changes in Trigeminal Ganglion Macrophages Enhance Orofacial Ectopic Pain After Inferior Alveolar Nerve Injury
Age-related Changes in Trigeminal Ganglion Macrophages Enhance Orofacial Ectopic Pain After Inferior Alveolar Nerve Injury
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DOI：
10.21873/invivo.13062
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发表时间：
2023
期刊：
影响因子：
2.3
通讯作者：
S. Fujiwara;K. Urata;Tatsuki Oto;Yoshinori Hayashi;S. Hitomi;K. Iwata;T. Iinuma;M. Shinoda
中科院分区：
文献类型：
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作者：
S. Fujiwara;K. Urata;Tatsuki Oto;Yoshinori Hayashi;S. Hitomi;K. Iwata;T. Iinuma;M. Shinoda
摘要背景/目的：与下牙槽神经（IAN）损伤相关的异位疼痛已被报道涉及三叉神经节（TG）中的巨噬细胞表达。然而，与年龄相关的变化对这种异常疼痛状况的影响仍然未知。本研究旨在阐明TG中巨噬细胞表达和表型转化与年龄相关的变化的参与，以及这些变化如何增强IAN横切（IANX）后的异位机械性异常性疼痛。材料与方法：我们使用了加速衰老小鼠（SAM）-倾向8（SAMP 8）和SAM-抗性1（SAMR 1）小鼠，它们通常用于研究衰老相关的变化。在轻度麻醉下对须垫皮肤施加机械刺激;在IANX后21 d测量机械头退缩阈值（MHWT）。随后，我们对支配须垫皮肤的TG中的Iba 1（巨噬细胞标志物）-免疫反应（IR）细胞、Iba 1/CD 11 c（M1样炎症巨噬细胞标志物）-co-IR细胞和Iba 1/CD 206（M2样抗炎巨噬细胞标志物）-co-IR细胞的数量进行计数。在向IANX处理的SAMP 8小鼠连续TG内施用脂质体氯膦酸盐Clophosome®-A（LCCA）后，检查胡须垫皮肤的MHWT值。结果：IANX后5天，与SAMR 1-小鼠相比，SAMP 8小鼠的MHWT显著降低。IANX后5 d，SAMP 8小鼠的Iba 1-IR和Iba 1/CD 11 c-co-IR细胞计数显著高于SAMR 1小鼠。与对照LCCA给药相比，LCCA给药显著恢复了MHWT。结论：IANX后胡须垫皮肤的异位机械性异常性疼痛因衰老而加剧，这涉及TG中M1样炎性巨噬细胞的增加。
Abstract Background/Aim: The ectopic pain associated with inferior alveolar nerve (IAN) injury has been reported to involve macrophage expression in the trigeminal ganglion (TG). However, the effect of age-related changes on this abnormal pain conditions are still unknown. This study sought to clarify the involvement of age-related changes in macrophage expression and phenotypic conversion in the TG and how these changes enhance ectopic mechanical allodynia after IAN transection (IANX). Materials and Methods: We used senescence-accelerated mouse (SAM)-prone 8 (SAMP8) and SAM-resistance 1 (SAMR1) mice, which are commonly used to study ageing-related changes. Mechanical stimulation was applied to the whisker pad skin under light anaesthesia; the mechanical head withdrawal threshold (MHWT) was measured for 21 d post-IANX. We subsequently counted the numbers of Iba1 (macrophage marker)-immunoreactive (IR) cells, Iba1/CD11c (M1-like inflammatory macrophage marker)-co-IR cells, and Iba1/CD206 (M2-like anti-inflammatory macrophage marker)-co-IR cells in the TG innervating the whisker pad skin. After continuous intra-TG administration of liposomal clodronate Clophosome®-A (LCCA) to IANX-treated SAMP8-mice, the MHWT values of the whisker pad skin were examined. Results: Five days post-IANX, the MHWT had significantly decreased in SAMP8 mice compared to SAMR1-mice. Iba1-IR and Iba1/CD11c-co-IR cell counts were significantly increased in SAMP8 mice compared to SAMR1 mice 5 d post-IANX. LCCA administration significantly restored MHWT compared to control-LCCA administration. Conclusion: Ectopic mechanical allodynia of whisker pad skin after IANX is exacerbated by ageing, which involves increases in M1-like inflammatory macrophages in the TG.