Osteoporosis in Light of a New Mechanism Theory of Delayed Onset Muscle Soreness and Non-Contact Anterior Cruciate Ligament Injury

Osteoporosis is a disorder, with a largely unknown pathomechanism, that is often marked as a "silent thief", because it usually only becomes undisguised when fractures occur. This implies that the pathological damage occurs earlier than the sensation of pain. The current authors put forward a non-contact injury model in which the chronic overloading of an earlier autologously microinjured Piezo2 ion channel of the spinal proprioceptor terminals could lead the way to re-injury and earlier aging in a dose-limiting and threshold-driven way. As a result, the aging process could eventually lead the way to the metabolic imbalance of primary osteoporosis in a quad-phasic non-contact injury pathway. Furthermore, it is emphasised that delayed onset muscle soreness, non-contact anterior cruciate injury and osteoporosis could have the same initiating proprioceptive non-contact Piezo2 channelopathy, at different locations, however, with different environmental risk factors and a different genetic predisposition, therefore producing different outcomes longitudinally. The current injury model does not intend to challenge any running pathogenic theories or findings, but rather to highlight a principal injury mechanism

A térd mozgásközéppontjának közelítése geometriai úton - esettanulmány

Az elmúlt időszakban megjelent elmélet a nem-kontakt elülső keresztszalag sérülést két fázisú sérülésnek írja le. Ennek értelmében az elsődleges proprioceptív idegvég sérülés nem megszokott vagy kimerítő excentrikus izomkontrakciók kivitelezése közben alakulhat ki, amikor a fáradtsággal járó mozgás fenntartása akut stressz hatást is kivált. A másodlagos sérülés a propriocepció elsődleges károsodásának következtében kialakuló nagyobb és több szövetet érintő károsodás. A kutatás célja egy mozgásvizsgálaton alapuló geometriai módszer kidolgozása és alkalmazhatóságának ellenőrzése, amely a térd mozgásközéppontjának helyét az adott mozgás minden időpillanatában az alsó végtag kijelölt anatómia pontjainak térbeli helyzetéből geometriai úton számítja. A közelítést az adott mozgás minden időpillanatában az alsó végtag kijelölt anatómia pontjainak térbeli helyzetének segítségével tettük meg. A mozgásvizsgálat bemutatása egy elülső keresztszalag (LCA) műtött személyen történt. A kijelölt anatómiai pontokra helyezett markerek térbeli helyzetét rögzítettük, amelyekből különböző mozgásparamétereket számoltunk, mint a térdízület flexio-extensio szöge, a tibia frontális irányból vett relatív dőlésszöge. Feltételezzük, hogy az eredő erő támadáspontja (továbbiakban térdpont) jó közelítéssel a tibia tengely és a térd síkjának speciálisan meghatározott egyenesének metszéspontja. A vizsgált személy esetén az egészséges alsó végtag térdpontja leérkezés során a tibia belső fejének irányába tolódott, mely arra utalhat, hogy a leérkezés során az eredő erő támadáspontja a tibiában a proximalis tibia mediális része felé tolódott. A méréseink kiindulópontot jelenthetnek további mérésekhez, mely során az eredő erő támadáspontjának helyét a nem-kontakt elülső keresztszalag sérülés új elmélete értelmében vizsgálják

Disrupted Neural Regeneration in Dry Eye Secondary to Ankylosing Spondylitis - With a Theoretical Link between Piezo2 Channelopathy and Gateway Reflex, WDR Neurons, and Flare-Ups

This study aimed at analyzing the corneal neural regeneration in ankylosing spondylitis patients using in vivo corneal confocal microscopy in correlation with Langerhans cell density, morphology, and dry eye parameters. Approximately 24 ankylosing spondylitis subjects and 35 age- and gender-matched control subjects were enrolled. Data analysis showed that all corneal nerve-fiber descriptives were lower in the ankylosing spondylitis group, implicating disrupted neural regeneration. Peripheral Langerhans cell density showed a negative correlation with nerve fiber descriptions. A negative correlation between tear film break-up time and corneal nerve fiber total branch density was detected. The potential role of somatosensory terminal Piezo2 channelopathy in the pathogenesis of dry eye disease and ankylosing spondylitis is highlighted in our study, exposing the neuroimmunological link between these diseases. We hypothesized earlier that spinal neuroimmune-induced sensitization due to this somatosensory terminal primary damage could lead to Langerhans cell activation in the cornea, in association with downregulated Piezo1 channels on these cells. This activation could lead to a Th17/Treg imbalance in dry eye secondary to ankylosing spondylitis. Hence, the corneal Piezo2 channelopathy-induced impaired Piezo2-Piezo1 crosstalk could explain the disrupted neural regeneration. Moreover, the translation of our findings highlights the link between Piezo2 channelopathy-induced gateway to pathophysiology and the gateway reflex, not to mention the potential role of spinal wide dynamic range neurons in the evolution of neuropathic pain and the flare-ups in ankylosing spondylitis and dry eye disease

CD3+/CD56+ NKT-like Cells Show Imbalanced Control Immediately after Exercise in Delayed-Onset Muscle Soreness

The purpose of the study was to carry out an immunophenotypical characterization with a special focus on natural killer cells of junior swimmers from the Hungarian National Swim Team before and after an intensive acute exercise. Nineteen swimmers, ten females and nine males, completed the exercise protocol. Sixteen swimmers experienced delayed-onset muscle soreness. Most of our findings substantiated earlier results, such as the increase in the percentage of the CD3−/CD56+ natural killer cells and the CD3−/CD56dim+ NK cells, and the decrease in the percentage of CD3+ T cells among lymphocytes after the exercise protocol. The drop of natural killer cell activity back to the pre-exercise level was in line with earlier findings. Interestingly, the percentage of CD3+/CD56+ NKT-like cells did not change significantly in those three swimmers who did not report delayed-onset muscle soreness. On the contrary, the percentage of CD3+/CD56+ NKT-like cells among lymphocytes increased in fourteen and decreased in two swimmers reporting delayed-onset muscle soreness. This study for the first time demonstrated a link between the delayed-onset muscle soreness and the imbalanced control of CD3+/CD56+ NKT-like cells among lymphocytes. However, validation of this association in a larger sample size study will be necessary

LF Power of HRV Could Be the Piezo2 Activity Level in Baroreceptors with Some Piezo1 Residual Activity Contribution

Heart rate variability is a useful measure for monitoring the autonomic nervous system. Heart rate variability measurements have gained significant demand not only in science, but also in the public due to the fairly low price and wide accessibility of the Internet of things. The scientific debate about one of the measures of heart rate variability, i.e., what low-frequency power is reflecting, has been ongoing for decades. Some schools reason that it represents the sympathetic loading, while an even more compelling reasoning is that it measures how the baroreflex modulates the cardiac autonomic outflow. However, the current opinion manuscript proposes that the discovery of the more precise molecular characteristics of baroreceptors, i.e., that the Piezo2 ion channel containing vagal afferents could invoke the baroreflex, may possibly resolve this debate. It is long known that medium- to high-intensity exercise diminishes low-frequency power to almost undetectable values. Moreover, it is also demonstrated that the stretch- and force-gated Piezo2 ion channels are inactivated in a prolonged hyperexcited state in order to prevent pathological hyperexcitation. Accordingly, the current author suggests that the almost undetectable value of low-frequency power at medium- to high-intensity exercise reflects the inactivation of Piezo2 from vagal afferents in the baroreceptors with some Piezo1 residual activity contribution. Consequently, this opinion paper highlights how low-frequency power of the heart rate variability could represent the activity level of Piezo2 in baroreceptors

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

Psoriasis is considered a multifactorial and heterogeneous systemic disease with many underlying pathologic mechanisms having been elucidated; however, the pathomechanism is far from entirely known. This opinion article will demonstrate the potential relevance of the somatosensory Piezo2 microinjury-induced quad-phasic non-contact injury model in psoriasis through a multidisciplinary approach. The primary injury is suggested to be on the Piezo2-containing somatosensory afferent terminals in the Merkel cell–neurite complex, with the concomitant impairment of glutamate vesicular release machinery in Merkel cells. Part of the theory is that the Merkel cell–neurite complex contributes to proprioception; hence, to the stretch of the skin. Piezo2 channelopathy could result in the imbalanced control of Piezo1 on keratinocytes in a clustered manner, leading to dysregulated keratinocyte proliferation and differentiation. Furthermore, the author proposes the role of mtHsp70 leakage from damaged mitochondria through somatosensory terminals in the initiation of autoimmune and autoinflammatory processes in psoriasis. The secondary phase is harsher epidermal tissue damage due to the primary impaired proprioception. The third injury phase refers to re-injury and sensitization with the derailment of healing to a state when part of the wound healing is permanently kept alive due to genetical predisposition and environmental risk factors. Finally, the quadric damage phase is associated with the aging process and associated inflammaging. In summary, this opinion piece postulates that the primary microinjury of our “sixth sense”, or the Piezo2 channelopathy of the somatosensory terminals contributing to proprioception, could be the principal gateway to pathology due to the encroachment of our preprogrammed genetic encoding

Delayed Onset Muscle Soreness (DOMS): The Repeated Bout Effect and Chemotherapy-Induced Axonopathy May Help Explain the Dying-Back Mechanism in Amyotrophic Lateral Sclerosis and Other Neurodegenerative Diseases

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

Should We Void Lactate in the Pathophysiology of Delayed Onset Muscle Soreness? Not So Fast! Let’s See a Neurocentric View!

The pathophysiology of delayed onset muscle soreness is not entirely known. It seems to be a simple, exercise-induced delayed pain condition, but has remained a mystery for over 120 years. The buildup of lactic acid used to be blamed for muscle fatigue and delayed onset muscle soreness; however, studies in the 1980s largely refuted the role of lactate in delayed onset muscle soreness. Regardless, this belief is widely held even today, not only in the general public, but within the medical and scientific community as well. Current opinion is highlighting lactate’s role in delayed onset muscle soreness, if neural dimension and neuro-energetics are not overlooked. By doing so, lactate seems to have an essential role in the initiation of the primary damage phase of delayed onset muscle soreness within the intrafusal space. Unaccustomed or strenuous eccentric contractions are suggested to facilitate lactate nourishment of proprioceptive sensory neurons in the muscle spindle under hyperexcitation. However, excessive acidosis and lactate could eventually contribute to impaired proprioception and increased nociception under pathological condition. Furthermore, lactate could also contribute to the secondary damage phase of delayed onset muscle soreness in the extrafusal space, primarily by potentiating the role of bradykinin. After all, neural interpretation may help us to dispel a 40-year-old controversy about lactate’s role in the pathophysiology of delayed onset muscle soreness