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Neurobiology of Skin at a Glance
  • In an interactive network, cutaneous nerves communicate with various skin cells, the endocrine system, and the immune system.
  • Neurocutaneous interactions influence a variety of physiological and pathophysiological functions such as thermoregulation, cell growth, inflammation, host defense, apoptosis, pruritus, pain, metastasis, and wound healing.
  • Primary afferent as well as autonomic nerves release neuromediators and activate specific receptors on many target skin cells.
  • Cutaneous cells express a variety of specific receptors tightly controlled by upregulatory or downregulatory signals, peptidases, or neighboring receptors.
  • Many mediators (peptides, proteases, cytokines, kinins, prostanoids, opioids, cannabinoids, neurotrophins, etc.) are critically involved in physiological and pathophysiological conditions in the skin by activating neuronal receptors.
  • The spinal cord and CNS modulate transmitted signals from the peripheral nerves with respect to the perception of pain or itch, and—vice versa—modulate skin function.
  • New pathways are being defined for the treatment of various skin diseases in which the neuro-immuno-endocrine axis is implicated.

This chapter discusses the structural basis and the specific molecules involved in the interactions between the skin and different portions of the nervous system.

The peripheral nervous system provides essential information to the rest of body during injury of “danger signals” such as parasites, UV radiation, toxins, allergens, pH changes, or “stress”. This information can be modulated at various levels including the brain, spinal cord, dorsal root ganglia (DRG), peripheral sensory nerve endings, autonomic nerves and neurons, etc; and through specialized structures like Pacini bodies or specialized cells such as Merkel cells. This closely woven group of structures and their molecules are ultimately and critically involved in normal cutaneous biology and skin diseases (eTable 102-0.1). In conjunction with the spinal cord and the brain, peripheral sensory nerves have afferent functions; their endings detect physical stimuli such as touch, heat or cold, and chemical mediators into the skin from nerve endings and also have efferent functions in the skin. (eFig. 102-0.1). These sensory nerves critically contribute to skin development before birth and to protection and homeostasis after birth. In addition, autonomic nerves modulate both physiological and pathophysiological functions as part of the stress response to external or endogenous stimuli, and form a vital link communicating with the vascular, endocrine, and immune systems (eTable 102-0.1).

eTable 102-0.1 Physiological and Pathophysiological Functions of Sensory and Autonomic Nerves

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