interleukins), encouraging analgesia and pain modulation in chronic and even complex pain conditions [41, 91–93, 131]; Progenitor cell, mescenchymal stem cell, and growth factor proliferation (i.e., vascular endothelial growth factor, transforming growth factor β-1) [28, 35, 94–99] are all elements seen to assist with progenesis responses such as angiogenesis [49–70, 88–90, 97–99], osteogenesis [8, 12–22, 100–103], and tendogenesis [28–45, 94, 95].
Stimulokinetics of SWT
Stimulokinetics provide insights as to how forces (shear, tension, and compression) are detected and transduced by cells, which is then translated into regulatory signals. Any structure regardless of being inanimate or animate require the actions of physical forces on them. The constant attraction-repulsion force feedback loop acting on its atoms, allow all structures to hold their form, and perform their respective functions. Cells are considered to be the most essential and fundamental components of all living organisms, and were first closely investigated by Robert Hooke in the late 1600s. The principles of physics described in “Hooke’s Law” regarding the influence of force on matter would be later adapted into active force influences in cellular biology by Wilhelm His in the late 1800s. The detection and transcription of forces into biochemical signals are key fundamentals by which cells and organs maintain viability, stability and health [115–124]. The stimulokinetics and the ensuing translational responses of cells to force (stimulodynamics) are commonly termed as “mechanotransduction.” Over the past two decades, resurgence in the study of mechanobiology has provided greater insights of cellular responses to stimulus (forces), and its role in homeostasis and disease [115–124]. To be concise, mechanotransduction involves the communication and modulation of forces on molecular and cellular levels determining the cellular and organism’s fate. The cytoskeleton structure of mammalian cells are able to detect and translate forces in minute nano-Newton ranges, and play a pertinent role in homeostasis (i.e., stem cell differentiation) and in disease (i.e., neoplastic processes) [125–128]. Protein folding, bone shaping, muscle contraction and regeneration, hearing, touch, lung regulation, and circulatory pressure are all in principle regulated by transducers that sense, respond, or react to this mechanosensory feedback complex [115–124]. Although the exact mechanism and the complexities of mechanotransduction is yet to be fully elucidated, chemical signals and tensional translations of mechanical forces are considered as being a key precipitator of events [115–131] – example, fluid force (shear stress) influences arterial blood, traction force (tensional stress) influences cell migration, and membrane tension (tensional stress) influences muscle contraction channels, all with a unifying principle that these force-translation exchanges are linked to the extracellular matrix and the cytoskeleton by a network of specialized transducers [129–131] and receptor sites. Medical SWT is considered to exert its influence on tissue by means of stimulus translation via this mechanotransduction principle [77]. The high velocity supersonic force generated during SWT is transmitted into the target tissue where a nonviolent isotropic shear stress force occurs on cell membranes leading to microvesicle excuviations. The excuviated microvesicles carry potent cargo (i.e., proteins, nucleic acids) that stimulates neighboring cells by fusion, which in turn activates cellular communication and the biochemical and biocellular translational effects (Fig. 6).
Simultaneously these very same SW impulses exert a pressure spectrum that causes a contractile tensional force that acts on the integrin, and actin cytoskeleton complex of cells. Hence, the stimulus from SWT is seen to exert its influence on both the extra and intracellular matrix [77]. The translational effects of SWT on tissue are seen to influence a broad spectrum of endogenous biochemical and biological events (i.e., toll-like receptors, inflammatory markers, neurotransmitters, and progenesis factors) that have been known to engender homeostatic return and functional restoration [7, 8, 12–27, 35, 40, 41, 49, 50–59, 62–67, 88–103]. From what is presently known of the microenvironment (protein network and structural matrix composition) of cells, it becomes plausible to hypothesize the mechanotransduction principle of SWT force action on tissue, providing some clarity as to the stimulokinetics and stimulodynamics of SWT on cells. It is further plausible when considering the mechanics of action and the biological progenesis responses associated with SWs, to consider medical SWT as being an endogenous stem cell activation treatment modality [71, 72,
