Delayed onset muscle soreness (DOMS) is hypothesized to be caused by glutamate excitotoxicity-induced acute compression axonopathy of the sensory afferents in the muscle spindle. Degeneration of the same sensory afferents is implicated in the disease onset and progression of amyotrophic lateral sclerosis (ALS). A series of “silent” acute compression proprioceptive axonopathies with underlying genetic/environmental factors, damaging eccentric contractions and the non-resolving neuroinflammatory process of aging could lead to ALS disease progression. Since the sensory terminals in the muscle spindle could not regenerate from the micro-damage in ALS, unlike in DOMS, the induced protective microcircuits and their long-term functional plasticity (the equivalent of the repeated bout effect in DOMS) will be dysfunctional. The acute stress invoking osteocalcin, bradykinin, COX1, COX2, GDNF, PGE2, NGF, glutamate and N-methyl-D-aspartate (NMDA) receptors are suggested to be the critical signalers of this theory. The repeated bout effect of DOMS and the dysfunctional microcircuits in ALS are suggested to involve several dimensions of memory and learning, like pain memory, inflammation, working and episodic memory. The spatial encoding of these memory dimensions is compromised in ALS due to blunt position sense from the degenerating proprioceptive axon terminals of the affected muscle spindles. Dysfunctional microcircuits progressively and irreversibly interfere with postural control, with motor command and locomotor circuits, deplete the neuroenergetic system, and ultimately interfere with life-sustaining central pattern generators in ALS. The activated NMDA receptor is suggested to serve the “gate control” function in DOMS and ALS in line with the gate control theory of pain. Circumvention of muscle spindle-loading could be a choice of exercise therapy in muscle spindle-affected neurodegenerative diseases.

中文翻译：

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迟发性肌肉酸痛（DOMS）：反复发作和化学疗法诱发的轴索病可能有助于解释肌萎缩性侧索硬化症和其他神经退行性疾病的消退机制

延迟发作的肌肉酸痛（DOMS）被认为是由谷氨酸兴奋性毒性引起的肌梭感觉传入神经急性压迫性轴索病引起的。肌萎缩性侧索硬化症（ALS）的发病和进展与相同感觉传入的退化有关。一系列具有潜在遗传/环境因素的“沉默”急性压迫性本体轴突病，破坏性的离心收缩和衰老的非解决性神经炎症过程均可能导致ALS疾病进展。由于肌梭中的感觉末端无法从ALS的微损伤中再生，因此与DOMS不同，诱导的保护性微电路及其长期功能可塑性（等同于DOMS中的反复发作效应）将失去功能。提示骨钙蛋白，缓激肽，COX1，COX2，GDNF，PGE2，NGF，谷氨酸和N-甲基-D-天冬氨酸（NMDA）受体的急性应激是该理论的关键信号。有人建议，DOMS和ALS中微电路功能障碍的反复发作效应涉及记忆和学习的多个方面，例如疼痛记忆，炎症，工作和情节记忆。这些记忆尺寸的空间编码在ALS中受到损害，这是由于受影响的肌肉纺锤体退化的本体感受轴突末端产生的钝头位置感所致。功能失调的微电路会逐渐且不可逆地干扰姿势控制，运动指令和运动电路，耗尽神经能量系统，并最终干扰ALS中维持生命的中央模式发生器。建议激活的NMDA受体在DOMS和ALS中发挥“门控制”功能，这与疼痛的门控制理论相一致。在受肌肉纺锤影响的神经退行性疾病中，规避肌肉纺锤负荷可能是一种运动疗法。