Sympathetic signals beneath the surface: fresh insights from skin and muscle

The sympathetic branch of the autonomic nervous system, known for its governance of the "fight or flight" response, has attracted newfound interest due to its role in maintaining bodily homeostasis in various tissue types. Sympathetic activity in the skin is often perturbed in neurological and neurodegenerative disorders. Notably, aberrant changes in the sympathetic skin response can be detected before clinical manifestations of diabetic neuropathy. Furthermore, sympathetic signaling at neuromuscular junctions in skeletal muscle has now been demonstrated to be critical for synapse integrity and proper functioning. Insufficient sympathetic signaling in skeletal muscle underlies the pathogenesis of muscle weakness in several disease states, such as myasthenia syndromes and sarcopenia. Additionally, surgical sympathectomies, a treatment method for conditions that involve heightened sympathetic activity, can give rise to other unwanted side effects, prompting the need for sympathetic trunk reconstruction. Therefore, the sympathetic nervous system, with renewed appreciation of its known functions and developing excitement for its recently discovered functions, remains a source for a wealth of potential discoveries that can further enable us to improve human health.