Abstract
Background/Objectives: Cerebral palsy (CP) is a leading cause of motor disability in children and is commonly associated with spasticity. Treatment with radial extracorporeal shock waves (rESWs) is an established non-invasive therapy for spasticity, although its underlying mechanisms remain poorly understood. Caenorhabditis elegans (C. elegans) represents a powerful model for neuromuscular research due to its fully mapped nervous system, conserved cholinergic pathways and suitability for high-throughput behavioral analysis. This study aimed to test whether rESWs modulate cholinergic signaling at the neuromuscular junction (NMJ) in C. elegans. Methods: Wild-type and acr-16 mutant C. elegans were exposed in liquid to varying doses of rESWs, nicotine and carbachol in different combinations. Locomotor behavior was recorded using high-resolution video tracking, and parameters including peristaltic speed, body wavelength, reversals and omega bends were quantified. Results: Exposure to rESWs transiently altered locomotion, most notably by reducing forward speed and increasing the frequency of reversals. However, rESWs did not consistently modify behavioral responses to nicotine or carbachol, and these effects were not clearly dependent on NMJ-associated nicotinic receptors. Conclusions: Exploring C. elegans as a model for rESW effects on spasticity proved informative but also revealed important limitations. Results indicate that rESWs act on the nervous system more broadly, extending beyond neuromuscular structures. This contrasts with the clinical situation, where rESWs primarily target muscles and connective tissues. While this precludes C. elegans as a direct model for CP-related spasticity, the observation that rESWs influence nervous-system function at a systemic level points to potential therapeutic avenues for neurological diseases.