Central amygdala activation of extracellular signal-regulated kinase 1 and age-dependent changes in inflammatory pain sensitivity in mice.

Central amygdala activation of extracellular signal-regulated kinase 1 and age-dependent changes in inflammatory pain sensitivity in mice.
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DOI:
10.1016/j.neurobiolaging.2017.04.010
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发表时间:
2017-08
影响因子:
4.2
通讯作者:
Kolber BJ
Kolber BJ
中科院分区:
医学2区
文献类型:
--
作者:
Sadler KE;Gartland NM;Cavanaugh JE;Kolber BJ

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由于躯体感觉系统的改变,老年人对有害刺激更敏感。在这些实验中,我们检查了年轻,中年和老年小鼠在外周炎症期间的疼痛样行为,以确定临床前动物模型中是否存在相同的敏感性。受伤后,中年和老年小鼠比年轻小鼠表现出更多的自发性疼痛样行为,与临床人群中的疼痛患病率相匹配。中老年小鼠也在受伤的爪子中产生持续的机械超敏反应。此外,老年小鼠在未受伤的爪子机械超敏反应表明中枢伤害性系统的年龄依赖性变化。为了解决这一问题,研究了杏仁核(CeA)中央核中疼痛相关蛋白的表达,这是一个调节躯体疼痛的边缘脑区域。损伤后,在老年小鼠的右侧CeA中观察到细胞外信号调节激酶1(ERK 1)(一种具有已知伤害性功能的蛋白质)的磷酸化增加,而在中年或年轻动物中则没有。这些研究结果表明,年龄依赖性的变化,脊髓上的伤害性系统可能占增加疼痛样行为在老龄化人口。
Aging populations are more sensitive to noxious stimuli as a result of altered somatosensory systems. In these experiments, we examined pain-like behaviors in young, middle-aged, and old mice during peripheral inflammation to determine if the same sensitivity exists in pre-clinical animal models. Immediately following injury, middle-aged and old mice exhibited more spontaneous pain-like behaviors than young mice, matching pain prevalence in clinical populations. Middle-aged and old mice also developed persistent mechanical hypersensitivity in the injured paw. Furthermore, old mice developed mechanical hypersensitivity in the non-injured paw suggesting age-dependent changes in central nociceptive systems. To address this end, pain-related protein expression was examined in the central nucleus of the amygdala (CeA), a limbic brain region that modulates somatic pain. Following injury, increased phosphorylation of extracellular-signal regulated kinase 1 (ERK1), a protein with known nociceptive functions, was observed in the right CeA of old mice and not middle-aged or young animals. These findings suggest that age-dependent changes in supraspinal nociceptive systems may account for increased pain-like behaviors in aging populations.