Epimuscular myofascial force transmission: insights on BTX-A intervention and muscle spindle sensory feedback

Mechanical equilibrium between skeletal muscles is maintained via connective tissues that surround the musculoskeletal system as a continuum. Muscle contrac- tion generates forces that spread within the muscle compartment through connective tissues, facilitating epimuscular myofascial force transmission (EMFT). This thesis ex- plored mechanical and sensory implications of EMFT using in vivo animal experiments. First, the long-term effects of botulinum toxin type-A (BTX-A), a common spasticity management drug, on individual and intermuscular muscle mechanics was studied in rats. Although BTX-A-induced paralysis was sustained, findings contradicted clinical aims at the individual muscle level (e.g., 12% increase in passive forces in the injected muscle and narrowed range of force exertion in the non-targeted bi-articular muscle by 15% distally and 32% proximally). Importantly, unlike in acute observations, dimin- ished EMFT was not observed. Given its clinical relevance in spastic muscle mechanics, BTX-A's efficacy seems tied to its impact on EMFT. These studies highlighted complex and uncontrolled BTX-A effects on intermuscular mechanics, suggesting limitations in long-term outcomes for managing spasticity. Then, the influence of EMFT on muscle spindle (MS) sensory feedback was tested in mice. Synergistic muscle stimulation re- sulted in significant increase in MS afferent firing (53% on average) due to intermuscular mechanical interactions. Variability in MS responses indicated that MSs sense local length changes across the muscle that arise from muscle fiber-extracellular matrix in- teractions. Findings provided insights for optimizing spasticity management strategies and EMFT's role in sensorimotor integration.