Delayed Onset Muscle Soreness and Critical Neural Microdamage-Derived Neuroinflammation

Abstract

Piezo2 transmembrane excitatory mechanosensitive ion channels were identified as the principal mechanotransduction channels for proprioception. Recently, it was postulated that Piezo2 channels could be acutely microdamaged on an autologous basis at proprioceptive Type Ia terminals in a cognitive demand-induced acute stress response time window when unaccustomed or strenuous eccentric contractions are executed. One consequence of this proposed transient Piezo2 microinjury could be a VGLUT1/Ia synaptic disconnection on motoneurons, as we can learn from platinum-analogue chemotherapy. A secondary, harsher injury phase with the involvement of polymodal Aδ and nociceptive C-fibers could follow the primary impairment of proprioception of delayed onset muscle soreness. Repetitive reinjury of these channels in the form of repeated bout effects is proposed to be the tertiary injury phase. Notably, the use of proprioception is associated with motor learning and memory. The impairment of the monosynaptic static phase firing sensory encoding of the affected stretch reflex could be the immediate consequence of the proposed Piezo2 microdamage leading to impaired proprioception, exaggerated contractions and reduced range of motion. These transient Piezo2 channelopathies in the primary afferent terminals could constitute the critical gateway to the pathophysiology of delayed onset muscle soreness. Correspondingly, fatiguing eccentric contraction-based pathological hyperexcitation of the Type Ia afferents induces reactive oxygen species production-associated neuroinflammation and neuronal activation in the spinal cord of delayed onset muscle soreness.

Psoriasis, Is It a Microdamage of Our “Sixth Sense”? A Neurocentric View

“…Impairment of this vesicular release machinery could be one reason why glutamate is significantly elevated in the serum of patients with plaque psoriasis [ 81 ]. Accordingly, the author theorizes that the stress-induced impairment of prolonged static-phase firing and the Piezo2 channelopathy could lead to lost position control of cell orientation in the epidermis, as was hypothesized in the primary injury phase of DOMS [ 14 , 15 , 16 , 17 ]. Piezo2 channelopathy also means the impaired cross-talking between Piezo2 and Peizo1, as was suggested in DED [ 33 ].…”

“…The cross-talking of Type III and C fibers is due to the secondary harsher tissue damage, namely, in the muscle, connective tissue, or extracellular matrix (ECM). One proposed basis for this cross-talking is Piezo2-channel-based [ 15 , 17 , 33 , 54 ]. The chemical and enzymatic destruction of the ECM impairs Piezo2 mechanogating [ 22 ]; as a result, it could provide one way for the temporal summation of pain by nociceptive C-fibers in DOMS [ 14 , 17 , 86 ].…”

“…One proposed basis for this cross-talking is Piezo2-channel-based [ 15 , 17 , 33 , 54 ]. The chemical and enzymatic destruction of the ECM impairs Piezo2 mechanogating [ 22 ]; as a result, it could provide one way for the temporal summation of pain by nociceptive C-fibers in DOMS [ 14 , 17 , 86 ].…”

“…Hilton’s rule is suggested to lay the ground for the common sensory guiding of muscles, bones, and skin [ 14 , 15 ]. However, this sensory guidance not only serves the growth process and regeneration of muscles, bones, and skin, but also seems to play a critical role in remodeling [ 14 , 17 , 30 ].…”

“…The author of this manuscript suggests that the somatosensory afferent terminals of the Merkel cell–neurite complex could be microdamaged by repetitive forced longitudinal stretch under an acute or chronic stress response time window, as could be the case in delayed-onset muscle soreness (DOMS) [ 14 ]. Correspondingly, it is proposed that Piezo2 ion channels at the Merkel cell–neurite complex could be subjected to pathological mechano-energetic microdamage, and as a result could become “leaky” during allostatic stress, such as in DOMS [ 15 , 16 , 17 ]. Notably, the proposed types of sensory terminal lesions, named terminal arbor degeneration (TAD), evolve after a threshold-driven, dose-limiting manner in an acute and chronic fashion, not associated with Wallerian-like axonal degeneration [ 16 , 18 ].…”