Degeneration and recovery of the neuromuscular junction after application of extracorporeal shock wave therapy

Abstract

It is known that free nerve endings are degenerated after application of shock waves. We therefore hypothesized that the application of shock waves to muscle induces dysfunction of neuromuscular transmission at neuromuscular junctions. We investigated changes in neuromuscular transmission in response to shock wave application. Sprague-Dawley rats were used in this study. Two thousand shock waves at an energy flux density of 0.18 mJ/mm 2 were applied to their right calf muscles. Neuromuscular junctions of gastrocnemius muscles were evaluated using rhodamine-a-bungarotoxin on the day of treatment (n ¼ 5). Amplitude and latency of compound muscle action potentials were measured on the day of treatment and 1, 2, 4, 6, and 8 weeks after treatment (n ¼ 10, each group). Degenerated acetylcholine receptors existed in all treated muscles. Although the action potential amplitude on the treated side was significantly less than on the control side from the day of treatment (25.1 AE 7.8 vs. 34.5 AE 9.1, p ¼ 0.012) to 6 weeks (27.9 AE 7.2 vs. 34.5 AE 7.2, p ¼ 0.037), there was no significant difference at 8 weeks. There was no significant difference in transmission latency between the groups. Keywords: neuromuscular junction; extracorporeal shock wave therapy; compound muscle action potential; neuromuscular transmission; acetylcholine receptor Impaired muscle coordination of limbs afflicted with central nervous system dysfunctions such as cerebral infarction, cerebral palsy, and dystonia is very common. This impairment causes severe limitations of daily living 1,2 and affects patients for their lifetime. Injection of botulinum toxin to focal muscles decreases muscle tone and is effective in improving motor function for impaired muscle coordination of limbs.3,4 For the past 20 years, treatment using botulinum toxin has gained acceptance as a popular treatment. However, the treatment using botulinum toxin has several difficulties with complications including severe allergic reaction and asthenia.3 Moreover, economic considerations inhibit many patients from undergoing this treatment because of its high cost. Recently, it has been reported that extra corporal shock wave treatment (ESWT) is able to improve function without inducing weakness in patients who suffer from spasticity and dystonia. 5,6 However, the mechanism of its clinical effect in the treatment of spasticity and dystonia has not been clarified. It is known that free nerve endings and sensory nerve fibers are degenerated after the application of shock waves.7,8 Therefore, we hypothesized that the application of shock waves to muscles induces dysfunction of neuromuscular transmission at neuromuscular junctions (NMJs). The purpose of this study was to investigate the changes in NMJs in response to ESWT to clarify its mechanism in the treatment of spasticity and dystonia. MATERIALS AND METHODSSeventy, 8-week-old male Sprague-Dawley rats (Japan SLC, Shizuoka, Japan) were used in this study. Animals were housed in an animal resources facility. Their room was mai...

Extracorporeal shock wave treatment can selectively destroy end plates in neuromuscular junctions

“…This increased density of AChRs thickens the postsynaptic membrane, which may change the acoustic impedance between the presynaptic and postsynaptic membranes. In addition, we previously confirmed the degeneration of AChRs after rESW exposure . Therefore, the high density of AChRs at the end plate may explain why the effect of rESW exposure is confined to end plates.…”

“…Using the results of our previous report (difference in mean amplitude, 10.0 mV; SD, 7.0), we calculated the sample size required to show a significant reduction in CMAP amplitude with a statistically significant P value of 0.05 and power of 0.80. This analysis indicated that more than 9 limbs per group were required, so we measured the CMAP in 10 rats.…”

“…In a previous study, we applied radial extracorporeal shock waves (rESWs) to the gastrocnemius muscle of Sprague-Dawley rats and discovered, using a rhodamine-a-bungarotoxin binding method, that rESW-exposed muscles exhibited degeneration of acetylcholine receptors (AChRs). 5 Compared with controls, rESW-exposed muscles showed significantly reduced compound muscle action potential (CMAP) amplitudes immediately after treatment, which persisted for 8 weeks without delaying latency. These results suggest that ESWT had caused a transient dysfunction in nerve conduction at the neuromuscular junction (NMJ).…”

The Effect of Extracorporeal Shock Wave Therapy on Lower Limb Spasticity in Subacute Stroke Patients

“…Previous studies explained the mechanism as the effect of the generation of nitric oxides [14], the effect on spinal cord excitability [15], the effect of mechanical vibration [15], the effect on the golgi tendon organ [10], or the passive stiffness of muscles determined by inactive connective tissues [8]. Considering the known fact that the nitric oxides generated by ESWT involve the formation of neuromuscular junctions in the peripheral nervous system and play important roles in neurotransmission, memories, and synaptic plasticity in the central nervous system [16,17] along with a recent report from an interesting study conducted with rats indicating that spasticity was relived because neuromuscular transmission was hindered by ESWT in neuromuscular junctions [18], nitric oxides seem to play core roles in spasticity-relieving mechanisms. Because F-wave and H-reflex related variables showed no differences between before and after treatment in previous studies in which the neurophysiological evaluations were conducted, the effect on spinal cord excitability appears to be small [8,9].…”

Effect of Different Energy Levels of Radial Shock Wave Therapy on Spasticity in Patients With Stroke

“…Kenmoku et al observed rapid degeneration of acetylcholine receptors after SWT application and pointed out that these consequences were very similar to those of a neuromuscular transmission inhibitor like botulinum toxin. However, unlike botulinum toxin, no obvious weakness in the target muscle [34]. Chronic spasticity itself would further worsen joint resistance through fibrosis of inactive connective tissue due to structural and mechanical changes in the muscle [35].…”