Muscle cramps as disorders of impaired termination of contraction: An integrated neurophysiological framework

Muscle cramps are common neuromuscular phenomena observed across diverse clinical and physiological settings, including hemodialysis and exercise. Although altered motor neuron excitability is considered a central mechanism, the physiological processes underlying the persistence and termination of cramp activity remain incompletely understood. This narrative review integrates neurophysiological, metabolic, and peripheral physiological evidence to propose an integrated framework for muscle cramp persistence, with particular emphasis on sustained motor unit activity, inhibitory control, calcium handling, and energetically supported relaxation processes. Current evidence suggests that sustained motor unit activity and altered spinal inhibitory control represent key mechanisms underlying muscle cramps. In addition, metabolically stressed conditions, altered calcium handling, impaired energetic support for ATP-dependent relaxation processes, and altered cross-bridge kinetics may contribute to inefficient termination of contraction. These interacting neural, metabolic, and peripheral physiological factors may help explain the persistence and variability of cramp activity across different clinical contexts. Muscle cramps may be better understood not simply as disorders of excessive activation, but as conditions involving impaired termination of contraction arising from interacting neurophysiological and metabolic mechanisms. This integrated framework may provide a useful conceptual and physiological basis for future mechanistic and translational investigation.