Bradykinin and Nerve Growth Factor Play Pivotal Roles in Muscular Mechanical Hyperalgesia after Exercise (Delayed-Onset Muscle Soreness)
Bradykinin and Nerve Growth Factor Play Pivotal Roles in Muscular Mechanical Hyperalgesia after Exercise (Delayed-Onset Muscle Soreness)
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DOI：
10.1523/jneurosci.3803-09.2010
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发表时间：
2010-03-10
影响因子：
5.3
通讯作者：
Mizumura, Kazue
中科院分区：
文献类型：
--
作者：
Murase, Shiori;Terazawa, Etsuji;Mizumura, Kazue
不习惯的剧烈运动，包括延长收缩（LC）往往会导致延迟发作的肌肉酸痛（DOMS），一种肌肉机械痛觉过敏。引起这种现象的物质在很大程度上是未知的。特别的是，DOMS在运动期间和运动后不久都不会被感知到，而是在近似1天后才被感知到。使用B-2缓激肽受体拮抗剂HOE 140，我们在这里显示，缓激肽释放在运动过程中起着关键作用，触发过程中，导致肌肉机械痛觉过敏。HOE 140在LC前注射时完全抑制肌肉机械性痛觉过敏的发生，但在LC后2天注射时未能逆转已经发生的机械性痛觉过敏。无论何时注射B-1拮抗剂均无效。上调神经生长因子（NGF）的mRNA和蛋白质发生在运动肌肉在一个可比的时间过程（12小时至2天后LC）的肌肉机械痛觉过敏。运动后2天肌肉注射NGF抗体可逆转肌肉机械性痛觉过敏。HOE 140抑制NGF的上调。相反，缩短收缩或拉伸既不引起机械性痛觉过敏，也不上调神经生长因子。缓激肽与缩短收缩，但不是单独缓激肽，再现持久的机械痛觉过敏。我们还表明，大鼠神经生长因子敏感的细纤维传入机械刺激后，在周边10-20分钟。因此，通过激活B-2缓激肽受体的神经生长因子上调是必不可少的（虽然不令人满意）的机械痛觉过敏运动后。目前的观察结果解释了为什么DOMS发生延迟，为什么延长收缩而不是缩短收缩诱导DOMS。
Unaccustomed strenuous exercise that includes lengthening contraction (LC) often causes delayed-onset muscle soreness (DOMS), a kind of muscular mechanical hyperalgesia. The substances that induce this phenomenon are largely unknown. Peculiarly, DOMS is not perceived during and shortly after exercise, but rather is first perceived after similar to 1 d. Using B-2 bradykinin receptor antagonist HOE 140, we show here that bradykinin released during exercise plays a pivotal role in triggering the process that leads to muscular mechanical hyperalgesia. HOE 140 completely suppressed the development of muscular mechanical hyperalgesia when injected before LC, but when injected 2 d after LC failed to reverse mechanical hyperalgesia that had already developed. B-1 antagonist was ineffective, regardless of the timing of its injection. Upregulation of nerve growth factor (NGF) mRNA and protein occurred in exercised muscle over a comparable time course (12 h to 2 d after LC) for muscle mechanical hyperalgesia. Antibodies to NGF injected intramuscularly 2 d after exercise reversed muscle mechanical hyperalgesia. HOE 140 inhibited the upregulation of NGF. In contrast, shortening contraction or stretching induced neither mechanical hyperalgesia nor NGF upregulation. Bradykinin together with shortening contraction, but not bradykinin alone, reproduced lasting mechanical hyperalgesia. We also showed that rat NGF sensitized thin-fiber afferents to mechanical stimulation in the periphery after 10-20 min. Thus, NGF upregulation through activation of B-2 bradykinin receptors is essential (though not satisfactory) to mechanical hyperalgesia after exercise. The present observations explain why DOMS occurs with a delay, and why lengthening contraction but not shortening contraction induces DOMS.