Abstract
Nerves are subjected to tensile forces in various paradigms such as injury and regeneration, joint movement, and rehabilitation treatments, as in the case of neurodynamic treatment (NDT). The NDT induces selective uniaxial repeated tension on the nerve and was described to be an effective treatment to reduce pain in patients. Nevertheless, the biological mechanisms activated by the NDT promoting the healing processes of the nerve are yet still unknown. Moreover, a dose–response analysis to define a standard protocol of treatment is unavailable. In this study, we aimed to define in vitro whether NDT protocols could induce selective biological effects on sensory and motor neurons, also investigating the possible involved molecular mechanisms taking a role behind this change. The obtained results demonstrate that NDT induced significant dose-dependent changes promoting cell differentiation, neurite outgrowth, and neuron survival, especially in nociceptive neurons. Notably, NDT significantly upregulated PIEZO1 gene expression. A gene that is coding for an ion channel that is expressed both in murine and human sensory neurons and is related to mechanical stimuli transduction and pain suppression. Other genes involved in mechanical allodynia related to neuroinflammation were not modified by NDT. The results of the present study contribute to increase the knowledge behind the biological mechanisms activated in response to NDT and to understand its efficacy in improving nerve regenerational physiological processes and pain reduction.
Highlights
Nerves are subjected to tensile forces in various paradigms such as injury and regeneration, joint movement, and rehabilitation treatments, as in the case of neurodynamic treatment (NDT)
The differentiation ratio was significantly higher in NSC-34 cells treated with both Low Repetitions (LR) and High Repetitions (HR) protocols (Fig. 1B, Table 1 Supplementary for statistical analysis) than in cells belonging to CTR IN or control out” (CTR OUT) groups
Similar results were detected in 50B11 cells with a significantly higher differentiation rate in LR and HR protocols compared to CTR IN and CTR OUT groups (Fig. 1B, Table 1 Supplementary for statistical analysis)
Summary
Nerves are subjected to tensile forces in various paradigms such as injury and regeneration, joint movement, and rehabilitation treatments, as in the case of neurodynamic treatment (NDT). Despite the positive results obtained from clinical and preclinical studies that link NDT-induced pain reduction and allodynia improvement to changes in the peripheral and central nervous system, fundamental aspects to obtain standardized treatment protocols have not yet been defined. To overcome this lack of knowledge, the aim of the present research is threefold: (1) to define whether a single set of repeated mechanical stimuli could induce biological and morphological changes in neurons; (2) to define whether NTD could lead to negative effects on neurons and (3) to investigate whether those changes have a dose-dependent behavior. Not all the biological processes are shared among different species, in our research we focused on genes linked to neuropathic pain and stress mechanisms that are expressed in mice, rats, and humans[35,37,49,50,51]
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