Opinion Delayed-Onset Muscle Soreness Begins with a Transient Neural Switch, 2025, Sonkodi

Delayed-Onset Muscle Soreness Begins with a Transient Neural Switch
Sonkodi, Balázs

Unaccustomed and/or strenuous eccentric contractions are known to cause delayed-onset muscle soreness. In spite of this fact, their exact cause and mechanism have been unknown for more than 120 years. The exploration of the diverse functionality of the Piezo2 ion channel, as the principal proprioceptive component, and its autonomously acquired channelopathy may bring light to this apparently simple but mysterious pain condition.

Correspondingly, the neurocentric non-contact acute compression axonopathy theory of delayed-onset muscle soreness suggests two damage phases affecting two muscle compartments, including the intrafusal (within the muscle spindle) and the extrafusal (outside the muscle spindle) ones. The secondary damage phase in the extrafusal muscle space is relatively well explored. However, the suggested primary damage phase within the muscle spindle is far from being entirely known.

The current manuscript describes how the proposed autonomously acquired Piezo2 channelopathy-induced primary damage could be the initiating transient neural switch in the unfolding of delayed-onset muscle soreness. This primary damage results in a transient proprioceptive neural switch and in a switch from quantum mechanical free energy-stimulated ultrafast proton-coupled signaling to rapid glutamate-based signaling along the muscle–brain axis. In addition, it induces a transient metabolic switch or, even more importantly, an energy generation switch in Type Ia proprioceptive terminals that eventually leads to a transient glutaminolysis deficit and mitochondrial deficiency, not to mention a force generation switch.

In summary, the primary damage or switch is likely an inward unidirectional proton pathway reversal between Piezo2 and its auxiliary ligands, leading to acquired Piezo2 channelopathy.

Link | PDF (International Journal of Molecular Sciences) [Open Access]

 

Hungarian study @Wyva

I think there's interesting stuff here, although it takes me quite a bit of finding definitions of words to understand it.

e.g. this is from reference 22

References 22 and 23 are interesting in that the suggestion is that the extent of movement disability in some people treated with a chemotherapy drug isn't explained by peripheral neuropathy. At that point perhaps, the psychosomatic crowd might leap in to suggest that the movement disability is not caused by the drug, but instead by the trauma the cancer patient has experienced. But these references suggest that the prolonged disability is due to the sodium ion channels being blocked.

I think this is also interesting in relation to the loss of control, the clumsiness, that I experience with repeated muscle use and the hints that people with ME/CFS are unable to sustain the firing of motor neurons. We've also seen Na+ channels come up in theories of ME/CFS and in other conditions that I think may be related such as the chronic symptoms sometimes experienced from ciguatera and similar toxins.

I don't know how it all hangs together, but I think there are clues here.