TRPM8-mediated cutaneous stimulation modulates motor neuron activity during treadmill stepping in mice

Abstract

Motor units are generally recruited from the smallest to the largest following the size principle, while cutaneous stimulation has the potential to affect spinal motor control. We aimed to examine the effects of stimulating transient receptor potential channel sub-family M8 (TRPM8) combined with exercise on the modulation of spinal motor neuron (MN) excitability. Mice were topically administrated 1.5% icilin on the hindlimbs, followed by treadmill stepping. Spinal cord sections were immunostained with antibodies against c-fos and choline acetyltransferase. Icilin stimulation did not change the number of c-fos + MNs, but increased the average soma size of the c-fos + MNs during low-speed treadmill stepping. Furthermore, icilin stimulation combined with stepping increased c-fos + cholinergic interneurons near the central canal, which are thought to modulate MN excitability. These findings suggest that TRPM8-mediated cutaneous stimulation with low-load exercise promotes preferential recruitment of large MNs and is potentially useful as a new training method for rehabilitation.

The Impact of Milk Fat Globule Membrane with Exercise on Age-Related Degeneration of Neuromuscular Junctions

“…Immunostaining of the spinal cord was performed as described previously [ 28 ]. Briefly, the vertebral column containing the spinal cord was dissected and post-fixed in 4% paraformaldehyde overnight at 4 °C.…”

“…Immunostaining of the spinal cord was performed as described previously [28]. Briefly, the vertebral column containing the spinal cord was dissected and post-fixed in 4% paraformaldehyde overnight at 4 • C. The lower lumbar segments (L3-L5) of the spinal cords were isolated and impregnated with 30% sucrose in PBS for over 3 days at 4 • C, followed by embedding in OCT compound (Sakura Finetek Japan, Osaka, Japan) and stored at −80 • C. The spinal cords were sectioned to a thickness of 30 µm using a cryostat (Leica, Wetzlar, Germany).…”

Menthol-induced cutaneous stimulation combined with self-paced walking training improves knee extension performance in untrained older healthy females

“…35% maximal voluntary contraction) may increase muscle strength 9) . Cutaneous stimulation with skin cooling has also been shown to modulate polysynaptic neural pathways, and a neural connection between skin cold receptors (transient receptor potential melastatin 8: TRPM8) and the motor neuron pool has been observed [10][11][12] . Skin cooling over the working muscle, without reducing the temperature of the muscle, facilitates preferential recruitment of large motor neurons 10) and reduces the recruitment threshold of fast muscle fibers 12) .…”

“…Cutaneous stimulation with skin cooling has also been shown to modulate polysynaptic neural pathways, and a neural connection between skin cold receptors (transient receptor potential melastatin 8: TRPM8) and the motor neuron pool has been observed [10][11][12] . Skin cooling over the working muscle, without reducing the temperature of the muscle, facilitates preferential recruitment of large motor neurons 10) and reduces the recruitment threshold of fast muscle fibers 12) . Several previous studies have also demonstrated a change in motor unit (MU) recruitment pattern, and MU recruitment thresholds were lower during voluntary contractions through spinal afferent input with electrical stimulation 13) .…”

Dopamine stimulation of the septum enhances exercise efficiency during complicated treadmill running in mice

“…Higher exercise efficiency during certain intensity movements increases enjoyment during exercise and promotes motivation for further spontaneous exercise, which is needed to prevent the development of locomotive syndrome or sarcopenia. Exercise efficiency involves adaptations of the skeletal muscle metabolism, respiratory-cardiovascular system, hemodynamics and motor skills [4][5][6][7][8][9][10][11][12][13][14][15][16].…”