From mechanotransduction to manual therapy: advances in piezo/TRP channels and lumbar degeneration.

Degenerative lumbar spondylolisthesis and related lumbar instability involve more than segmental biomechanical imbalance. They also involve disturbed mechanotransduction mediated by mechanosensitive ion channels. This review brings together basic, mechanobiological, and clinical studies on Piezo1, Piezo2, and TRPV4 in the intervertebral disc, cartilage endplate, facet joint, ligamentum flavum, and sensory afferent system, and considers how manual therapy might affect segmental kinematics, load transfer, and the local microenvironment. Piezo1 is most often linked to load-driven amplification of inflammation, senescence, apoptosis, and fibrosis; Piezo2 is more closely tied to proprioceptive disturbance and mechanically evoked pain sensitization; and TRPV4 shows context-dependent effects shaped by loading pattern, osmotic milieu, and tissue state. Manual therapy may therefore influence Piezo/TRP-related mechanotransduction indirectly through changes in segmental motion, load distribution, and sensorimotor control, although direct evidence remains limited. The literature fits better with viewing manual therapy as a way of reshaping the mechanical microenvironment than as a molecular intervention that directly targets ion channels. Future work should test this working mechanistic model by linking standardized mechanical inputs to imaging, molecular, physiological, and symptom-based outcomes across the pathway from altered mechanics to biological responses and clinical benefit.