Specific C-Receptors for Itch in Human Skin

Abstract

In microneurography experiments 56 unmyelinated nerve fibers were studied in the cutaneous branch of the peroneal nerve of healthy volunteers. Units were identified with the "marking" technique as mechanically and heat-responsive (CMH; n ϭ 30), heat-responsive (CH; n ϭ 13), or unresponsive to mechanical and heat stimulation (CM i H i ; n ϭ 13). None of the units showed spontaneous activity.These units were tested for responsiveness to iontophoresis of histamine (1 mA, 20 sec) from a small probe (diameter, 6 mm), which induced itch sensations lasting several minutes. Twenty-three units were unresponsive to histamine, and 25 units responded weakly with a few spike discharges after iontophoresis.Eight units, however, responded with sustained discharges to histamine, and their discharge patterns were matching the time course of the itch sensations. All C-units in this group were mechanically insensitive, and five of them were heat-responsive. They had very low conduction velocities of only 0.5 m/sec, on average, which is significantly lower than conduction velocities of the "polymodal" CMH units. This slow conduction velocities attributable to small axon diameters may be one reason why these units have not been encountered in previous studies. Histaminesensitive C-units had very large innervation territories extending up to a diameter of 85 mm on the lower leg.We conclude that these C-fibers represent a new class of afferent nerve fibers with particularly thin axons but excessive terminal branching. This type of C-fiber probably represents the afferent units long searched for mediating itch sensations.

Analysis of cellular and behavioral responses to imiquimod reveals a unique itch pathway in transient receptor potential vanilloid 1 (TRPV1)-expressing neurons

“…In general, C-fibers have been thought to be involved primarily in nociception. However, as more has been learned about C-fibers, it is increasingly evident that they also appear to mediate itch produced by various types of pruritogens (1)(2)(3)(4). Electrophysiological recording experiments in human skin showed the presence of a small subset of histamine-sensitive fibers among heterogeneous C-fiber nociceptors (1).…”

Ondansetron Treatment in a Child Presenting with Chronic Intractable Pruritus

“…A subset of afferent unmyelinated C-fibres innervating the skin called mechanoinsensitive and histamine-release nerve fibres transmit itch (10,11). Itch impulses are transmitted from the ipsilateral dorsal horn of the spinal cord through these itch-specific C-fibres to synapse with itch-specific secondary neurons.…”

Histamine and Antihistamines / Histamin i antihistamini

“…Most of the changes in allergic disease occur as a consequence of binding histamine to H1 receptor (38)(39)(40)54). Hypotension, tachycardia, flushing and headache occur through both the H1 and H2 receptors (55), whereas irritation of the skin in the form of itching and nasal congestion can be caused by the activation of H1 and H3 receptors (56,57).…”