When muscles lose neural drive, they atrophy rapidly. Neuromuscular electrical stimulation (NMS) has been used in attempts to prevent or reverse the atrophy, but optimal stimulation programs and parameters are not well defined. In this study, we investigated the effects of four different stimulation patterns on disuse atrophy produced in the tibialis anterior, lateral gastrocnemius, and soleus muscles of rats paralyzed with tetrodotoxin for seven days. Stimulation paradigms differed from one another by their stimulation frequency (2 or 10 pulses/s) and by their stimulation period (2 or 10 h a day). Results showed that stimulation with 2 pulses/s, paradigms were more effective at preventing disuse muscle atrophy than higher-frequency stimulation. The most marked difference was in the slow soleus muscle, which had only 10% mean atrophy when stimulated at 2 pulses/s for 10 h, compared to 26% atrophy when stimulated at 10 pulses/s for either 2 or 10 h and 32% atrophy in unstimulated, paralyzed controls. The level of atrophic change was not correlated with the levels of serum creatine kinase, used as an index of muscle damage. Results suggest that remediation of disuse atrophy may be accomplished using unphysiologically low rates of motor-unit activation despite the relatively low force produced by such unfused contractions. This may have significant implications for the design of therapies for muscle paralysis consequent to upper-motoneuron lesions.

Previous studies have shown that immobilization causes muscle atrophy and that the rate of atrophy depends on the length at which the muscle is immobilized. However, most studies have been carried out in neurologically intact animals that were capable of generating at least some voluntary muscle activation. In this study, tetrodotoxin was applied chronically to the rat sciatic nerve to produce complete paralysis of distal muscles for seven days, and the ankle was immobilized to hold the muscles at long or short lengths. Paralysis without immobilization resulted in relative weight losses of 36% for soleus, 19% for tibialis anterior (TA), and 17% for lateral gastrocnemius (LG) muscles. Casting the ankle in plantarflexion stretched TA and reduced its weight loss to 10%. Soleus and LG were shortened by this intervention and had increased losses of 43% and 28%, respectively. Fixing the limb in dorsiflexion resulted in a posture similar to that adopted by the unrestrained rats and had no significant effect on the amount of muscle atrophy compared to that in unrestrained paralyzed animals.