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

J Physiol Sci. 2019 Nov;69(6):931-938. doi: 10.1007/s12576-019-00707-3. Epub 2019 Sep 3.

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.

Keywords: Motor neuron; Somatosensory; Spinal cord; TRPM8; c-fos.

MeSH terms

  • Animals
  • Exercise Test
  • Gene Expression Regulation / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Neurons / physiology*
  • Physical Conditioning, Animal*
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • Pyrimidinones / pharmacology*
  • Skin / drug effects
  • TRPM Cation Channels / genetics
  • TRPM Cation Channels / metabolism*

Substances

  • Proto-Oncogene Proteins c-fos
  • Pyrimidinones
  • TRPM Cation Channels
  • TRPM8 protein, mouse
  • icilin