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Neuropeptides, itch, pruritus, prurigo, psoriasis, atopic dermatitis, substance P, histamine, sensory nerves



  • The nervous system of the skin has multiple functions:

    • Collecting and transmitting environmental information on touch, pain, pruritus and temperature to the brain.

    • Reacting to ligands that induce nerve activation by the antidromic release of neuropeptides and initiation of vascular and inflammatory reactions.

    • Communication with various skin cells, including those in the immune and endocrine systems.

    • Because of these, it also has a role in maintaining skin homeostasis and processes including thermoregulation, cell growth, inflammation, host defense mechanisms, apoptosis, and wound healing.

    • In pathological conditions, the nervous system is involved in the maintenance of pruritus, pain, and inflammatory skin diseases (eg, psoriasis vulgaris, atopic dermatitis).


The skin has a dense sensory network enabling human beings to sense different ranges and qualities of pain, pruritus, mechanical stimuli (eg, touch and vibration), and temperature. These senses have a role in the nonverbal communication among humans and also serve as protective mechanisms as they organize sensations taken from the environment that are sent to the brain. The brain not only plays a critical role in the perception of these sensations but also in their interpretation as pleasant, unpleasant, dangerous, or harmless. The skin contains a dense cutaneous sensory and autonomic network designed to sense these stimuli that also communicates with surrounding skin cells and has a bidirectional communication network within the central nervous system (CNS). This complex network is known to play a central role in the development of chronic pain and, as recently discovered, also in chronic pruritus. The latter constitutes a novel research area and is a major focus of this chapter.



Barring the stratum corneum, the entirety of the human skin is innervated. The nerves that innervate the skin, apart from the face, consist of cutaneous branches of musculocutaneous nerves that segmentally arise from the spinal nerves. Branches of trigeminal nerves in the facial tissue are responsible for its innervation. At the dermal subcutaneous junction, the primary nerve trunks enter the subcutaneous fat tissue and divide, forming a branching network. This nerve plexus supplies the vasculature, adnexal structures, and encapsulated sensory nerves (eg, Pacinian corpuscles). The nerve fibers subsequently rearrange into small nerve bundles, which, together with the blood and lymphatic vessels, form a network of interlaced nerves both beneath and within the epidermis (Fig. 21-1).1,2 Sensory and autonomic nerve fibers constitute cutaneous nerve fibers. Afferent impulses are conducted from the periphery of sensory nerves to cell bodies in the dorsal root ganglia (DRG) and to the trigeminal ganglion in the face. Because of their unipolar nature, one branch of a cutaneous sensory neuron’s single axon extends from their cell body towards the periphery, ...

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