ASIC3 Is Required for Development of Fatigue-Induced Hyperalgesia.
ASIC3 Is Required for Development of Fatigue-Induced Hyperalgesia.
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DOI：
10.1007/s12035-014-9055-4
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发表时间：
2016-03
影响因子：
5.1
通讯作者：
Sluka, Kathleen A.
中科院分区：
文献类型：
--
作者：
Gregory, Nicholas S.;Brito, Renan G.;Oliveira Fusaro, Maria Claudia G.;Sluka, Kathleen A.
剧烈的运动会加剧疼痛，阻碍人们参加常规运动和日常活动。急性运动引起疼痛的潜在机制还知之甚少。我们假设，在肌肉疲劳过程中，质子积累会激活肌肉伤害性感受器上的ASIC3，从而产生痛觉过敏。我们利用遗传学和药理学方法研究了ASIC3在疲劳增强型痛觉过敏模型中的作用。该模型使用两次向肌肉注射pH 5.0的生理盐水，并在第二次注射酸之前对同一肌肉产生电诱导的疲劳，以诱导机械性痛觉过敏。我们发现在电刺激6分钟后，肌肉力量和肌肉pH值显著降低。利用基因敲除小鼠的ASIC3基因缺失和用APETx2在肌肉中药物阻断ASIC3可以防止疲劳增强的痛觉过敏。而ASIC3型−/−小鼠和APETX2对疲劳反应无影响。令人惊讶的是，利用表达miRNA的HSV-1基因缺失支配肌肉的初级传入肌肉中的ASIC3，对痛觉过敏的发展没有影响。肌肉疲劳增加了肌肉中巨噬细胞的数量，用氯屈膦酸盐脂质体去除肌肉中的巨噬细胞可以防止疲劳增强型痛觉过敏的发展。因此，这些数据表明，疲劳降低肌肉中的pH，随后激活巨噬细胞上的ASIC3，以增强对肌肉侮辱的痛敏。
An acute bout of exercise can exacerbate pain, hindering participation in regular exercise and daily activities. The mechanisms underlying pain in response to acute exercise are poorly understood. We hypothesized that proton accumulation during muscle fatigue activates ASIC3 on muscle nociceptors to produce hyperalgesia. We investigated the role of ASIC3 using genetic and pharmacological approaches in a model of fatigue-enhanced hyperalgesia. This model uses two injections of pH 5.0 saline into muscle in combination with an electrically-induced fatigue of the same muscle just prior to the second injection of acid to induce mechanical hyperalgesia. We show a significant decrease in muscle force and decrease in muscle pH after 6 minutes of electrical stimulation. Genetic deletion of ASIC3 using knockout mice and pharmacological blockade of ASIC3 with APETx2 in muscle prevents the fatigue-enhanced hyperalgesia. However, ASIC3−/− mice and APETx2 have no effect on the fatigue response. Genetic deletion of ASIC3 in primary afferents innervating muscle using an HSV-1 expressing miRNA to ASIC3 surprisingly had no effect on the development of the hyperalgesia. Muscle fatigue increased the number of macrophages in muscle, and removal of macrophages from muscle with clodronate liposomes prevented the development of fatigue-enhanced hyperalgesia. Thus, these data suggest that fatigue reduces pH in muscle that subsequently activates ASIC3 on macrophages to enhance hyperalgesia to muscle insult.
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影响因子：
4.9
作者：
Gong W;Kolker SJ;Usachev Y;Walder RY;Boyle DL;Firestein GS;Sluka KA
通讯作者：
Sluka KA
DOI：
10.1523/jneurosci.3795-08.2008
发表时间：
2008-12-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Binshtok AM;Wang H;Zimmermann K;Amaya F;Vardeh D;Shi L;Brenner GJ;Ji RR;Bean BP;Woolf CJ;Samad TA
通讯作者：
Samad TA
DOI：
10.1016/j.bbrc.2005.09.054
发表时间：
2005-11-11
影响因子：
3.1
作者：
Jahr, H;van Driel, M;van Leeuwen, JPTM
通讯作者：
van Leeuwen, JPTM
影响因子：
25
作者：
Immke, DC;McCleskey, EW
通讯作者：
McCleskey, EW
影响因子：
--
作者：
Gautam M;Benson CJ;Ranier JD;Light AR;Sluka KA
通讯作者：
Sluka KA