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Skeletal muscle atrophy, deconditioning, and decreased function are consequences of skeletal muscle unloading induced by reduced physical activity, bed rest, and space flight. Reduced sensory input, particularly from the plantar surfaces of the feet, is one of the earliest consequences of unloading. This has been hypothesized to be a key factor in modulating the negative effects of unloading, especially those observed in the anti-gravity muscles of the lower limbs. Mechanical stimulation of the plantar surface during unloading to provide sensory input has been investigated as a potential means of attenuating unloading-induced muscle deconditioning. Results from human and animal models, including space flight, dry immersion, and hindlimb suspension, demonstrated that plantar stimulation evokes an increase in neuro-sensory activity and attenuates some elements of skeletal muscle deconditioning. The physiological mechanism(s) responsible for the protective effects of plantar stimulation in unloaded muscle, especially its anti-atrophic effects, have yet to be fully elucidated. Previous studies suggest that plantar stimulation might result in the release of growth hormone (GH) in response to increased afferent sensory nerve traffic induced by plantar stimulation. Since increased levels of circulating GH results in the activation of several different hypertrophic signaling pathways within skeletal muscle, it is possible that the anti-atrophic effects of plantar stimulation during unloading are mediated by GH.

The purpose of this dissertation project was to develop a system that delivers plantar stimulation to human subjects in a controlled manner and to investigate whether plantar stimulation results in the release of GH during acute skeletal muscle unloading (supine rest). Specifically, we hypothesized that GH concentrations would increase during acute unloading when subjects received 10 min of plantar stimulation to the right forefoot. Further, we hypothesized that the GH response would be augmented when subjects received plantar stimulation that activated muscle and joint proprioceptors as well as cutaneous mechanoreceptors compared to plantar pressures which stimulated only cutaneous mechanoreceptors. Thirteen healthy subjects participated in three sessions in random order: (1) control (or sham) condition in which the subjects received no stimulation; (2) 10-min plantar stimulation to the right forefoot with no support for the feet (stimulating cutaneous mechanoreceptors only); and (3) 10-min plantar stimulation to the right forefoot with the feet supported with the ankle at ~90° (stimulating cutaneous mechanoreceptors and muscle/joint proprioceptors). After 20 min of rest, subjects received either no stimulation or 10 min of stimulation. During the stimulation periods, force equivalent to 25% of body weight was applied cyclically by inflating and deflating an air bladder situated under the foot. Within each cycle, the bladder was inflated for 0.4 sec and deflated for 1.2 sec to simulate the frequency of forces applied during a normal walking pace (5.6 km/h). Force at the feet (pressure sensing insoles), muscle activity of the lower leg (surface electromyography, sEMG), and circulating immuno-assayable GH (venipuncture) were measured before, during, and after the plantar stimulation or sham period. Plantar stimulation with or without foot support did not affect immuno-assayable GH concentration or an aggregate measure of muscle activity (root mean square, RMS) compared to the control condition. Thus, immuno-assayable GH and sEMG appear not to have a role in the prevention of muscle atrophy during unloading. Other skeletal muscle growth factors should be considered. Continued work to understand the mechanism(s) responsible for the anti-atrophic effects of plantar stimulation may aid in the treatment of subjects who are bedridden, individuals who cannot regularly perform exercise due to an orthopedic or other medical condition and astronauts during space flight either as a supplement to current countermeasures or in place of them when countermeasure hardware is not available.



Spaceflight, Bed rest, Unloading, Muscle atrophy, Muscles, Growth hormone