Low maternal licking/grooming stimulation increases pain sensitivity in male mouse offspring.

Low maternal licking/grooming stimulation increases pain sensitivity in male mouse offspring.
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DOI:
10.1538/expanim.20-0030
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发表时间:
2021-02-06
影响因子:
2.4
通讯作者:
Kikusui T
Kikusui T
中科院分区:
医学4区
文献类型:
--
作者:
Sakamoto T;Ishio Y;Ishida Y;Mogi K;Kikusui T

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剥夺母亲护理与后代对疼痛的敏感性较高有关。在本研究中,我们假设母亲的舔/梳理行为是疼痛调节系统发展的重要因素。为了检验这一假设,我们使用了早期断奶 (EW) F1 母鼠的雄性 F2 后代,这些小鼠表现出较低的舔/梳理行为频率。福尔马林测试显示,EW F1 母鼠的 F2 后代表现出比正常断奶 (NW) F1 母鼠的 F2 后代显着更高的疼痛行为。我们发现,EW F1 母鼠的 F2 后代的腰骶背根神经节 (DRG) 中伤害感受器瞬时受体电位香草酸 1 (TRPV1) 的 mRNA 水平高于 NW F1 母鼠的 F2 后代,这表明较高的疼痛敏感性可能归因于较少的舔/梳理,这可能导致伤害性神经元的发育变化。在 DRG 中,Mas 相关 G 蛋白偶联受体 B4 (MrgprB4) 的 mRNA 水平在 EW F1 母鼠的 F2 后代中也上调,该受体是检测轻柔抚摸的感觉神经元的标记。考虑到轻柔的触摸可以减轻疼痛,Mrgprb4 的上调可能反映了一种代偿性变化。目前的研究结果表明,母亲的舔/梳理行为对疼痛调节系统的发展具有重要影响。
Deprivation of maternal care has been associated with higher pain sensitivity in offspring. In the present study, we hypothesized that the maternal licking/grooming behavior was an important factor for the development of the pain regulatory system. To test this hypothesis, we used male F2 offspring of early-weaned (EW) F1 mother mice that exhibit lower frequency of licking/grooming behavior. The formalin test revealed that F2 offspring of EW F1 dams showed significantly higher pain behavior than F2 offspring of normally-weaned (NW) F1 dams. We found that the mRNA levels of transient receptor potential vanilloid 1 (TRPV1), a nociceptor, were higher in the lumbosacral dorsal root ganglion (DRG) of F2 offspring of EW F1 dams than those of F2 offspring of NW F1 dams, suggesting that the higher pain sensitivity may be attributed to low licking/grooming, which may result in developmental changes in nociceptive neurons. In the DRG, mRNA levels of Mas-related G-protein coupled receptor B4 (MrgprB4), a marker of sensory neurons that detect gentle stroking, was also up-regulated in the F2 offspring of EW F1 dams. Considering that gentle touch alleviates pain, Mrgprb4 up-regulation may reflect a compensatory change. The present findings indicate important implications of maternal licking/grooming behavior in the development of the pain regulatory system.
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