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Extrafusal and intrafusal muscle effects in experimental botulinum toxin-A injection
R L Rosales1, K Arimura, S Takenaga
1Third Department of Internal Medicine, Kagoshima University School of Medicine, Kagoshima, Japan.
Abstract:
The effects of botulinum toxin-A was compared on both extrafusal and intrafusal muscle fibers in the biceps femoris of Wistar rats. Four days after injection no action potentials were elicited with stimulation single-fiber electromyography on the injected side. Fourteen days after injection, jitter became measurable and these values were increased on the injected side. Extrafusal muscle fibers began to atrophy on the 4th day and this continued to the 14th day postinjection. Atrophy was also evident and progressive in intrafusal muscle fibers. Increased terminal innervation ratios, end-plate spread of cholinesterase, and increased density of very small myelinated fibers in large intramuscular nerves were observed 14 days postinjection. Both extrafusal and intrafusal fibers are cholinergically innervated, and both were progressively affected by botulinum toxin, perhaps varying in degree only. In addition to partial denervation, Botulinum toxin effects in dystonia may also be related to modified spindle afferent discharge.
Insights
Botulinum toxin-A affects both extrafusal and intrafusal muscle fibers, causing atrophy and altered nerve function. These findings suggest botulinum toxin
Area of Science:
- Neurology
- Muscle Physiology
- Pharmacology
Background:
- Botulinum toxin-A is widely used for muscle spasticity.
- Its precise effects on different muscle fiber types and neural components are not fully understood.
Purpose of the Study:
- To investigate the differential effects of botulinum toxin-A on extrafusal and intrafusal muscle fibers.
- To elucidate the impact of botulinum toxin-A on neuromuscular transmission and muscle spindle function.
Main Methods:
- Single-fiber electromyography was used to assess neuromuscular activity in Wistar rats.
- Muscle fiber atrophy was evaluated morphologically.
- Histochemical and morphometric analyses were performed on nerve terminals and intramuscular nerves.
Main Results:
- Botulinum toxin-A injection led to a complete loss of action potentials in extrafusal fibers initially.
- Increased jitter and progressive atrophy were observed in both extrafusal and intrafusal fibers.
- Histological changes included increased terminal innervation ratios and end-plate abnormalities.
Conclusions:
- Both extrafusal and intrafusal muscle fibers are targets of botulinum toxin-A, with progressive and potentially differential effects.
- Botulinum toxin-A induces partial denervation and may alter muscle spindle afferent discharge, impacting its therapeutic role in conditions like dystonia.