Effects of Electrical Stimulation on the Prolongation of Botulinum Toxin Type A Induced Paralysis

Lee, Eun Ha; Kim, Sei Joo

Abstract

OBJECTIVE
Botulinum toxin works at the neuromuscular junction by inhibiting the release of acetylcholine from the presynaptic membrane. It has been indicated for limb spasticity in patients with upper motor neuron lesions. The paralytic effect of this toxin usually lasts for 3 to 4 months, and repeated injections are needed to maintain the effect. This study was performed to investigate whether electrical stimulation can prolong the paralytic effect induced by botulinum toxin type A. METHOD: Ninety male Sprague-Dawley rats, 30 for control and 60 for experimental, were studied. Botulinum toxin type A (Dysport ) was injected into the gastrocnemius muscle in the experimental groups (10 units for group 1 and 5 units for group 2), and normal saline 0.05 ml was injected into the same muscle in the control group. Thirty minutes of electrical stimulation was applied to the injected muscle with surface-stimulating electrodes. The stimulation was given once a day for 3 times in subgroup E1 and once every other day for 6 times in subgroup E2. No electrical stimulation was applied to subgroup N. Amplitudes of action potentials were measured serially on the injected muscles. At the third week, hematoxylin-eosin stained sections and synaptophysin immunohistochemical stained sections were examined.
RESULTS
1) At the second week after the toxin injection, amplitudes of action potentials maximally declined to 2.1~3.7% in group 1 and to 4.0~5.3% in group 2, compared to the initial amplitude. The amplitudes were beginning to recover from the third week. 2) Electrically stimulated groups demonstrated significantly more depressed amplitudes than non-stimulated group N. These effects lasted till week 2~4. 3) Hematoxylin-eosin staining for muscle sections showed degenerative changes of muscle fibers. Synaptophysin immunoreactivity in the muscle demonstrated multiple synaptophysin-positive areas in a muscle fiber of the toxin injected muscle.
CONCLUSION
Transient electrical stimulation to the botulinum toxin injected muscles seems to enhance the paralytic effects of the toxin.