Hormonal and molecular effects of restraint stress on formalin-induced pain-like behavior in male and female mice.
Hormonal and molecular effects of restraint stress on formalin-induced pain-like behavior in male and female mice.
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DOI：
10.1016/j.physbeh.2016.08.009
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发表时间：
2016-10-15
影响因子：
2.9
通讯作者：
Kolber BJ
中科院分区：
文献类型：
--
作者：
Long CC;Sadler KE;Kolber BJ
在应激事件期间抑制疼痛（应激诱导镇痛（SIA））的进化优势是显而易见的，但这种疼痛减轻表达的性别差异背后的原因却并不明显。男性和女性整合生理应激反应和下行疼痛抑制的不同方式尚不清楚。压力诱导镇痛的潜在脊髓上调节器是杏仁核（CeA）的中央核。这个大脑边缘区域参与压力和疼痛的处理。 CeA 在解剖学和分子学上与下丘脑垂体肾上腺 (HPA) 轴和下行疼痛网络区域相关。 CeA 对压力和疼痛的反应表现出基于性别的差异，这可能会在男性和女性中不同地诱发 SIA。在这里，我们检查了有害刺激后 SIA 行为和分子指数的性别差异。在足底注射福尔马林（一种有毒炎症剂）之前，对雄性和雌性小鼠进行急性束缚应激。注射福尔马林后 60 分钟测量自发性疼痛样行为，并在注射后 120 和 180 分钟评估机械超敏反应。束缚压力改变了雄性和雌性小鼠福尔马林诱导的自发行为以及雄性小鼠福尔马林诱导的机械超敏反应。为了评估 SIA 的分子指数，在 180 分钟时间点收集了来自 CeA 的组织样本和血液样本。束缚应激可防止雄性 CeA 中福尔马林诱导的细胞外信号调节激酶 2 (ERK2) 磷酸化增加，但在雌性中，福尔马林或束缚未观察到与 pERK2 相关的变化。注射后 180 分钟血浆皮质酮浓度也存在性别差异。这些结果表明，小鼠急性应激的行为、分子和激素指数存在性别差异，这种差异在应激和有害刺激后持续 180 分钟。
The evolutionary advantages to the suppression of pain during a stressful event (stress-induced analgesia (SIA)) are obvious, yet the reasoning behind sex-differences in the expression of this pain reduction are not. The different ways in which males and females integrate physiological stress responses and descending pain inhibition are unclear. A potential supraspinal modulator of stress-induced analgesia is the central nucleus of the amygdala (CeA). This limbic brain region is involved in both the processing of stress and pain; the CeA is anatomically and molecularly linked to regions of the hypothalamic pituitary adrenal (HPA) axis and descending pain network. The CeA exhibits sex-based differences in response to stress and pain that may differentially induce SIA in males and females. Here, sex-based differences in behavioral and molecular indices of SIA were examined following noxious stimulation. Acute restraint stress in male and female mice was performed prior to intraplantar injections of formalin, a noxious inflammatory agent. Spontaneous pain-like behaviors were measured for 60 min following formalin injection and mechanical hypersensitivity was evaluated 120 and 180 min post-injection. Restraint stress altered formalin-induced spontaneous behaviors in male and female mice and formalin-induced mechanical hypersensitivity in male mice. To assess molecular indices of SIA, tissue samples from the CeA and blood samples were collected at the 180 min time point. Restraint stress prevented formalin-induced increases in extracellular signal regulated kinase 2 (ERK2) phosphorylation in the male CeA, but no changes associated with pERK2 were seen with formalin or restraint in females. Sex differences were also seen in plasma corticosterone concentrations 180 min post injection. These results demonstrate sex-based differences in behavioral, molecular, and hormonal indices of acute stress in mice that extend for 180 min after stress and noxious stimulation.