Itch In Human Skin Research Articles

A novel missense mutation in oncostatin M receptor beta causing primary localized cutaneous amyloidosis.

Primary localized cutaneous amyloidosis (PLCA) is a chronic skin disorder, caused by amyloid material deposition in the upper dermis. Autosomal dominant PLCA has been mapped earlier to pathogenic missense mutations in the OSMR gene, which encodes the oncostatin M receptor ß subunit (OSMRß). OSMRß is interleukin-6 family cytokine receptors and possesses two ligands, oncostatin M and interleukin-31, which both have biologic roles in inflammation and keratinocyte cell proliferation, differentiation, and apoptosis. Here, we identified a new OSMR mutation in a Kurdish family for the first time. Blood samples were taken from all the affected individuals in the family. DNA extraction was performed using salting out technique. Primers were designed for intron flanking individual exons of OSMR gene which were subjected to direct sequencing after PCR amplification for each sample. Sequencing showed a C/T substitution at position 613 in the proband. This mutation results in an L613S (leucine 613 to serine) amino acid change. The identified mutation was observed in all affected family members but not in 100 ethnically matched healthy controls. Elucidating the molecular basis of familial PLCA provides new insight into mechanisms of itch in human skin and may lead to new therapeutic targets for pruritus.

Mechanically evoked itch in humans

When a newly developed experimental method to vibrate vellus hairs on human skin was applied to the face and arm in healthy subjects, intense itch was reproducibly induced on the face, but not on the arm, without any flare reactions. In contrast to histamine-induced itch, mechanically evoked itch was not characterized as burning or stinging by any subjects, and was resistant to histamine H1-receptor antagonists. When the stimulation was continued for 10min, mechanically evoked itch reached the maximum intensity within 10s, but gradually attenuated after 60 to 90s and was rarely perceivable at the end of stimulation. When the stimulation was discontinued at 90s, mechanically evoked itch rapidly attenuated after the end of stimulation, but took more than 10min before it completely diminished. These results indicate a possible involvement of C-tactile neurons in mechanically evoked itch because they have consistent characteristics such as low mechanical thresholds, intermediate adaptation, after discharge, favorable response to slowly moving stimuli, and fatigue during repeated mechanical stimulation, although it needs to be confirmed by future microneurographic studies. Touch-alloknesis was present in the adjacent skin area until mechanically evoked itch completely diminished, supporting the hypothesis that itch sensitization can be caused by a continuous activation of peripheral itch neurons whether or not they are histamine-sensitive C nerves. In conclusion, this study provides direct evidence of mechanosensitive nerves involved in itch in human skin. The purity of mechanically evoked itch without any pain-related sensory components is a major advantage for investigating the differentiation of itch from pain.

Nedocromil sodium inhibits histamine-induced itch and flare in human skin.

This study was designed to test the hypothesis that nedocromil sodium inhibits sensory nerve function to reduce flare and itch in human skin. Nedocromil sodium (2%) or water (control) was introduced into the volar forearm skin of eight non-atopic volunteers by iontophoresis (8 mC) and histamine (20 microl of 1 microM and 300 nM) injected intradermally 10 min later at the same site. Itch was assessed on a visual analogue scale every 20 s for 5 min. Weal and flare areas and mean blood flux within the flare were assessed by scanning laser Doppler imaging at 10 min. The results showed that nedocromil sodium reduced itch scores, totalled over 5 min, by approximately 74.0% (P<0.005) and flare areas by approximately 65% (P<0.03). Neither weal areas nor blood flux within were reduced. These data demonstrate that nedocromil sodium is effective in reducing neurogenic itch and flare in the skin. We suggest that its mechanism of action is modulation of sensory neurone activation or conduction in the skin.

Specific C-Receptors for Itch in Human Skin

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 = 30), heat-responsive (CH; n = 13), or unresponsive to mechanical and heat stimulation (CMiHi; n = 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. Histamine-sensitive 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.

Initiation of the effects of acrivastine and cetirizine on histamine/induced wheals and itch in human skin.

The initiation of the antihistamine effect of a single dose of acrivastine (8 mg) or cetirizine (10 mg) on wheals and itch induced by histamine dihydrochloride (10 mg/ml) in the prick test was studied in a randomized cross-over design employing 20 healthy medical students. The prick test was performed before ingestion of the drug and after 15, 20, 25, 30, 60 and 90 min and 2, 3 and 4 h. Local symptoms (itching) were recorded on a visual analogue scale. The inhibitory effect of acrivastine on the histamine wheal was first noticed 20 min (p < 0.01) after ingestion of the drug and that of cetirizine after 60 min (p < 0.001). The maximum effect of cetirizine, at 4 h, was greater than that of acrivastine, at 3 h (p < 0.001). The suppression of itching was first noticed 25 min after ingestion with both drugs.

Experimental itch in human skin elicited by rat mast cell chymase

No abstract available