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Neurophysiology of Pruritus Cutaneous Elicitation of Itch

Sonja Ständer, MD; Martin Steinhoff, MD, PhD; Martin Schmelz, MD, PhD; Elke Weisshaar, MD; Dieter Metze, MD; Thomas Luger, MD
Arch Dermatol. 2003;139(11):1463-1470. doi:10.1001/archderm.139.11.1463.
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Itching is defined as an unpleasant cutaneous sensation leading to the desire to scratch. It serves as a physiological self-protective mechanism as do other cutaneous sensations like pain, touch, vibration, cold, and heat to help defend the skin against harmful external agents. Pruritus can be evoked in the skin directly by mechanical and thermal stimuli or indirectly through chemical mediators. It may also be generated in the central nervous system independently of peripheral stimulation. Single-nerve-fiber recordings have shown that histamine-evoked itch is transmitted by selective slow-conducting subpopulations of unmyelinated C-polymodal neurons. Recent experimental studies using improved methods have demonstrated which of the suspected chemical itch mediators such as histamine, neuropeptides, prostaglandins, serotonin, acetylcholine, or bradykinin act pruritogenically on C-fibers. Moreover, investigations have revealed new receptor systems such as vanilloid, opioid, and cannabinoid receptors on cutaneous sensory nerve fibers that may modulate itch and thereby represent targets for antipruritic therapy. This review focuses on the peripheral generation of itch, including neurotransmitters, neuropeptides, and inflammatory mediators.

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Figure 1.

Increased and thickened dermal nerve fibers (arrows) in prurigo nodularis. The epidermis (E) shows irregular hyperplasia, and a dense inflammatory infiltrate (asterisk) can be seen in the dermis (immunohistochemical staining with anti-S100 protein antibody, original magnification ×200).

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Figure 2.

Immunofluorescence staining for cannabinoid 2 (CB2) receptor (A; fluoroscein isothiocyanate conjugated stain) and the axonal marker neurofilament (B; Texas red) in a cutaneous nerve of normal skin. Axons (arrows) and the perineurium (arrowheads) of a large dermal nerve fiber stain for CB2 receptor. C, Yellow staining (arrow) in an overlay of A and B indicates colocalization. (Original magnification ×600 for all photographs.)

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Figure 3.

Intraneuronal deposits of hydroxyethyl starch (HES). Monoclonal HES-specific antibody subjected to a postembedding immunogold technique and counterstained with uranyl acetate–lead citrate. Vacuoles (V) in the cytoplasm of a Schwann cell (C, core; A, axon) are immunoreactive (arrow) to anti-HES antibody (original magnification ×11 500).

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The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
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