BTX-A Administration to the Target Muscle Affects Forces of All Muscles Within an Intact Compartment and Epimuscular Myofascial Force Transmission

Abstract

Measurement of forces of mono- and bi-articular muscles of an entire intact muscle compartment can allow for a comprehensive assessment of the effects of Botulinum toxin type A (BTX-A) both at and beyond the injection site, and in conditions close to those in vivo. The goal was to test the hypotheses that BTX-A affects (1) the forces of not only the injected but also the noninjected muscles of the compartment, and (2) epimuscular myofascial force transmission (EMFT). Two groups of Wistar rats were tested: Control (no BTX-A injected) and BTX (0.1 units of BTX-A were injected exclusively to the mid-belly of TA). Isometric forces were measured simultaneously at the distal tendons of the tibialis anterior (TA) at different lengths, the restrained extensor digitorum longus (EDL) and the extensor hallucis longus (EHL) muscles and at the proximal tendon of EDL. Five days post-injection, BTX-A did affect the total forces of all muscles significantly: (1) The TA force decreased differentially (by 46.6%-55.9%) for most lengths such that a significant negative correlation was found between force reductions and increased muscle length. The maximum TA force decreased by 47.3%. However, the muscle's length range of force production did not change significantly. (2) Distal and proximal EDL forces decreased (on average by 67.8% and 62.9%, respectively). (3) The EHL force also decreased (on average by 9.2%). The passive forces of only the TA showed a significant increase at higher lengths. EMFT effects were shown for the control group: (1) at the shortest TA lengths, the EDL proximo-distal force differences were in favor of the distal force, which was reversed at higher lengths. (2) the EHL force measured at the shortest TA length decreased (by 34%) as a function of TA lengthening. After BTX-A exposure, such EMFT effects disappeared for the EDL, whereas they remained as profound for the EHL. Exposure to BTX-A does affect forces of all muscles operating in an intact compartment. For the BTX-A injected muscle, the reduction in muscle force becomes less pronounced at higher muscle lengths. BTX-A also has effects on EMFT, however, these effects are not uniform within the anterior crural compartment. Decreased forces of the noninjected synergistic muscles suggest the presence of unintended additional effects of BTX-A both for the targeted distal joint and for the nontargeted proximal joint.

Effects of botulinum toxin type A on non‐injected bi‐articular muscle include a narrower length range of force exertion and increased passive force

“…Yet, such data have more potential for improved understanding of effects of BTX‐A on joint mechanics. For example, reduction of active force is variable as a function of muscle length instead of being constant …”

“…showed that the force–length characteristics of both injected soleus and non‐injected plantaris muscles of the cat are affected by the toxin. Exclusive exposure of the tibialis anterior (TA) muscle of the anterior crural compartment of the rat also affects the forces of other muscles within the compartment, including extensor digitorum longus (EDL) and extensor hallucis longus (EHL) . On the other hand, it was also reported that passive forces of muscle exposed to BTX‐A show an increase .…”

Resistance to radial expansion limits muscle strain and work

“…To our knowledge, there are no studies to date that have measured intramuscular pressure in a fibrotic muscle, and therefore, we cannot rule out the possibility that increased IMP compensates for the increased resistance to radial expansion. Future work using pathological variation in the ECM (Smith et al 2011; Gao et al 2008; Järvinen et al 2002) or experimental manipulations of ECM stiffness (Yucesoy et al 2012; Turkoglu and Yucesoy 2016) will provide direct tests of the hypotheses generated by our study.…”

Botulinum toxin treatment of lower extremity spasticity

“…Так, в ряде работ показа-но, что моделирование по методу конечных элементов демонстрирует увеличение длины большинства сарко-меров по сравнению с идентичными саркомерами до начала терапии БТА [41]. Возникновение этого эффекта связывают с взаимодействием мышечных волокон и внеклеточного матрикса [42]. Эффект удли-нения саркомеров способствует повышению потенци-ала для создания активной мышечной силы в непара-лизованных частях мышцы и вызывает уменьшение диапазона длины, в котором мышца снижает свою силу в результате воздействия БТА, особенно сразу после повреждения.…”

“…Flexor hallucis longus 50 (40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50) Конфликт интересов. Авторы заявляют об отсутствии конфликта интересов.…”