The highest region of muscle spindle abundance should be the optimal target of botulinum toxin A injection to block muscle spasms in rats

Abstract

PurposeThe effective relief of muscle spasticity requires prompt solutions in rehabilitation medicine. This study aimed to reveal that the highest region of muscle spindle abundance is the optimal target of botulinum toxin A (BTX-A) injections for relieve muscle spasm.MethodsSixty adult, male Sprague–Dawley rats with lower limbs spasm caused by stroke after modeling, weighing (200 ± 20) g, were included in this study. The modelrats were divided into four groups: muscle spasm model group (group A), model rats treated with BTX-A injections into the middle of the muscle belly (group B), model rats treated with BTX-A injections into the center of the intramuscular nerve-dense region (INDR) (group C), and model rats treated with BTX-A injection into the center of the highest region of muscle spindle abundance (HRMSA) (group D). Groups B, C, and D were further divided into two subgroups: the 3rd and 6th days after BTX-A injection. The rats in each group were assigned modified Ashworth scale scores (MAS), and the changes in gastrocnemius muscle tone, wet muscle weight, and cross-sectional area of muscle fiber were detected.ResultsMuscle spindle abundance was the highest in the upper part of the INDR. Group B experienced no significant changes in MAS, muscle tone, wet muscle weight, or cross-sectional area of the muscle fiber. Conversely, groups C and D experienced a decrease in these indicators. Group C experienced the most significant decrease in wet muscle weight and cross-sectional area of muscle fibers. Group D experienced the most notable decrease in MAS and muscle tone. There were no significant differences in the indicators between the 3rd and 6th days after BTX-A injections in group B and there were significant differences in the improvement in the indicators between the two subgroups in groups C and D, with group D experiencing more notable intersubgroup differences.ConclusionThe efficacy of BTX-A injections into the HRMSA is significantly superior to that of conventional BTX-A injections into the middle of the belly muscle or the INDR in the treatment of muscle spasms. Hence, HRMSA should be the optimal target of BTX-A to relieve muscle spasms.

Division of neuromuscular compartments and localization of the center of the highest region of muscle spindles abundance in deep cervical muscles based on Sihler’s staining

“…The muscle spindles abundances obtained in this experiment were slightly higher than that in the mentioned study, possibly because of the uneven distribution of muscle spindles. This study focused on the INDR, which has a relatively large number of muscle spindles ( Yu et al, 2023 ). Present results indicate that the CRHMSA in the deep cervical muscle aligns with the center of the INDR.…”

“…Previous studies have reported that the intramuscular nerve dense region (INDR) location is consistent with the motor endplate band and can serve as an alternative target for BTX-A ( Amirali et al, 2007 ; Phadke et al, 2013 ). Other studies have indicated that the muscle spindle, a type of stretch receptor, is not uniformly distributed within the muscle ( Banks, 2006 ), with higher abundance in INDR and motor endplate bands ( Yu et al, 2023 ). After many central nervous system diseases (such as stroke), due to the weakened inhibition of upper motor neurons on the spinal cord, leading to increased excitability of alpha motor neurons, increased sensitivity of Ia type fibers and increased activity of gamma motor fibers in the muscle spindle, the hyperactive stretching reflex can be achieved through the α-γ loop, thereby exacerbating muscle spasms ( Phadke et al, 2013 ).…”

“…Maximizing BTX-A to block the intrafusal muscle fibers while minimizing its impact on extrafusal muscle fibers can improve the efficacy and rehabilitation quality of BTX-A for treating muscle spasms ( Phadke et al, 2013 ). Recent animal studies have confirmed that the center of the region of highest muscle spindle abundance (CRHMSA) in the INDR represents the optimal target for BTX-A to block muscle spasms ( Yu et al, 2023 ).…”

Division of neuromuscular compartments and localization of the center of the intramuscular nerve-dense region in pelvic wall muscles based on Sihler's staining

“…Therefore, accurate and appropriate BTX-A injection to the target site is essential. Studies have shown that 1 unit of BTX-A can infiltrate muscle tissue 1.5–3 cm 2 , and 2.5–5 units can diffuse into 4.5 cm 2 (Borodic et al 1994 ; Yu et al 2023 ). According to these theories and the results of this experiment, the INDR areas of the piriformis and obturator internus muscles are 5.37 ± 0.32 cm 2 and 13.33 ± 0.61 cm 2 , respectively.…”

Localisation of the centre of the highest region of muscle spindle abundance of anterior forearm muscles

“…Muscle spindles grow at different rates and are highly abundant in the INDR but are not uniformly distributed (Banks, 2006 ). Recent animal studies have demonstrated that the centre of the highest region of muscle spindle abundance (CHRMSA) in the INDR is the optimal target for BTX‐A to block muscle spasticity (Yu et al., 2023 ).…”