The potential mechanisms of exercise-regulated mechanically sensitive ion channels in promoting spinal cord injury repair: a hypothesis-driven narrative review

Abstract

Exercise training is a vital component of rehabilitation for individuals with spinal cord injury (SCI). However, its mechanisms of action remain unclear, which severely limits the development and implementation of precise exercise prescriptions for SCI. In this article, we propose a core hypothesis: mechanical stimulation generated by exercise is converted into key biological signals that regulate SCI repair through the activation of mechanosensitive channels (MSCs). To test this hypothesis, we adopt a narrative review approach to systematically integrate current evidence on MSCs including Piezo1, TRAAK/TREK-1, and TRPC1 in the contexts of neuroplasticity, bone and muscle homeostasis, and inflammatory responses. Based on this evidence, we construct a mechanistic framework linking specific MSCs to exercise-induced functional benefits, revealing the potential molecular logic by which exercise promotes spinal cord injury repair. As a hypothesis-driven narrative review, this article not only provides a theoretical foundation for developing quantifiable, personalized exercise prescriptions for SCI rehabilitation, but also outlines several testable research directions to facilitate experimental validation and clinical translation of the proposed hypothesis.