Inhibitory Regulation of Skeletal Muscle Shivering

Abstract

Skeletal muscle shivering thermogenesis contributes to the cold‐defensive maintenance of core body temperature and to the elevated body temperature during fever. The thermoregulatory reflex pathway through which skin and core cooling, or injection of prostaglandin E2 into the preoptic area of the hypothalamus, leads to activation of skeletal muscle shivering has been described (J Physiol 589.14: 3641–3658, 2011). Although this pathway influences the discharge of alpha‐motoneurons in the ventral horn, rather than sympathetic preganglionic neurons in the intermediolateral nucleus, it is remarkably parallel to the thermoregulatory pathway mediating cold‐defensive activation of brown adipose tissue (Cell Metabolism 19: 741‐756, 2014). To determine if this similarity extends to the central and vagal afferent inhibitory regulation of skeletal muscle shivering, neurons in the paraventricular hypothalamus, in the nucleus of the tractus solitarii, or in the ventrolateral medulla were activated; or electrical stimuli were applied to afferents in the cervical vagus nerve, during cold‐ or PGE2 injection‐evoked increases in masseter, neck and gastrocnemius muscle EMGs in Inactin‐anesthetized rats. Activation of neurons in each of these regions, or vagus nerve stimulation elicits a marked inhibition of cold‐evoked and PGE2‐evoked brown adipose tissue sympathetic outflow and thermogenesis. Overall, the results, indicate strong parallels between the inhibitory regulation of shivering and brown adipose tissue thermogenesis and energy consumption. The specific physiological stimuli for, and the synaptic integration sites supporting these inhibitions of shivering remain to be determined. Supported by NIH grant NS40987.