Sonkodi Balázs
Department of Health Sciences and Sport Medicine, University of Physical Education, Alkotas u. 44, H-1123 Budapest, Hungary.
Brain Sci. 2021 Jan 15;11(1):108. doi: 10.3390/brainsci11010108.
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.
延迟性肌肉酸痛（DOMS）被认为是由谷氨酸兴奋性毒性诱导的肌梭感觉传入神经急性压迫性轴索性神经病所致。相同感觉传入神经的退化与肌萎缩侧索硬化症（ALS）的疾病发生和进展有关。一系列具有潜在遗传/环境因素的“沉默”急性压迫性本体感觉轴索性神经病、损伤性离心收缩以及衰老过程中无法解决的神经炎症过程可能导致ALS疾病进展。与DOMS不同，由于ALS中肌梭的感觉终末无法从微损伤中再生，因此诱导的保护性微回路及其长期功能可塑性（相当于DOMS中的重复发作效应）将功能失调。引发骨钙素、缓激肽、COX1、COX2、GDNF、PGE2、NGF、谷氨酸和N-甲基-D-天冬氨酸（NMDA）受体的急性应激被认为是该理论的关键信号分子。DOMS的重复发作效应和ALS中功能失调的微回路被认为涉及记忆和学习的多个维度，如疼痛记忆、炎症、工作记忆和情景记忆。由于受影响肌梭退化的本体感觉轴突终末导致位置感觉迟钝，这些记忆维度的空间编码在ALS中受到损害。功能失调的微回路逐渐且不可逆地干扰姿势控制、运动指令和运动回路，耗尽神经能量系统，并最终干扰ALS中维持生命的中枢模式发生器。根据疼痛的闸门控制理论，激活的NMDA受体被认为在DOMS和ALS中发挥“闸门控制”功能。避免肌梭负荷可能是肌梭受影响的神经退行性疾病运动疗法的一种选择。
