Recent Studies of Cutaneous Nociception in Atopic and Non‐Atopic Subjects

Itching reflects a distinct quality of cutaneous nociception elicited by chemical or other stimuli to neuronal receptors at the superficial layers of the skin and muco‐cutaneous orifices. Although recent experimental studies of the conduction and perception of itch have yielded deeper insight into the physiology of this sensory quality, little is known about the neuromechanisms involved in pruritus accompanying many inflammatory skin diseases, in particular, in atopic eczema. Previous case‐control studies of our research group with patients suffering from atopic eczema (AE) revealed significantly diminished itch perception after iontophoretic application of different doses of histamine as well as substance P (i.c. injected). Further experiments using acetylcholine (ACh, i.c.) clearly demonstrated that ACh elicits pruritus instead of pain in patients with AE. The first part of the present review deals with the results of our most recent case‐control studies on histamine‐induced itch perception in atopics devoid of eczema as well as in patients with urticaria or psoriasis compared to atopics with or without manifest eczema. We demonstrated that both focal itch and perifocal alloknesis (i.e., itch elicited by a slight mechanical, otherwise non‐itching stimulus) were significantly reduced in eczema‐free atopics yet were normal in non‐atopics suffering from urticaria or psoriasis. In further studies using ACh i.c. injected into the uninvolved skin of patients with AE, lichen ruber, psoriasis, type IV contact eczema, or non‐specific nummular eczema (n=10/each group), all the atopics and 6/10 psoriatics felt itch instead of burning pain, but none of the others did. Different doses of vasoactive intestinal peptide (VIP) i.e. applied to the controls and the atopics with or without eczema did not markedly increase the intensity of nociceptive sensations. However, ACh induced pain in the controls, pure pruritus in the atopics with acute eczema, and a ‘mixture’ of pain and itch in the atopics just free from eczema. Obviously, the quality of sensations evoked by ACh and VIP depends on the inflammatory or non‐inflammatory state of the atopic skin. In a placebo‐controlled, double blind study on histamine‐induced focal itch and alloknesis with healthy subjects (n=15) using naltrexone (opioid receptor antagonist) and cetirizine (H1‐blocking agent), naltrexone was found to significantly reduce both itching and alloknesis. Cetirizine reduced focal itch but failed to influenc