Cowhage-Induced Itch as an Experimental Model for Pruritus. A Comparative Study with Histamine-Induced Itch

Histamine is the prototypical pruritogen used in experimental itch induction. However, in most chronic pruritic diseases, itch is not predominantly mediated by histamine. Cowhage-induced itch, on the other hand, seems more characteristic of itch occurring in chronic pruritic diseases.We tested the validity of cowhage as an itch-inducing agent by contrasting it with the classical itch inducer, histamine, in healthy subjects and atopic dermatitis (AD) patients. We also investigated whether there was a cumulative effect when both agents were combined.Fifteen healthy individuals and fifteen AD patients were recruited. Experimental itch induction was performed in eczema-free areas on the volar aspects of the forearm, using different itch inducers: histamine, cowhage and their combination thereof. Itch intensity was assessed continuously for 5.5 minutes after stimulus application using a computer-assisted visual analogue scale (COVAS).In both healthy and AD subjects, the mean and peak intensity of itch were higher after the application of cowhage compared to histamine, and were higher after the combined application of cowhage and histamine, compared to histamine alone (p<0.0001 in all cases). Itch intensity ratings were not significantly different between healthy and AD subjects for the same itch inducer used; however AD subjects exhibited a prolonged itch response in comparison to healthy subjects (p<0.001).Cowhage induced a more intense itch sensation compared to histamine. Cowhage was the dominant factor in itch perception when both pathways were stimulated in the same time. Cowhage-induced itch is a suitable model for the study of itch in AD and other chronic pruritic diseases, and it can serve as a new model for testing antipruritic drugs in humans

What causes itch in atopic dermatitis?

Itch, the hallmark of atopic dermatitis, has a significant impact on quality of life for patients with this disease. Various central and peripheral mediators have been suggested to play a role in the pathophysiology of atopic eczema itch. Significant cross-talk occurs among stratum corneum, keratinocytes, immune cells, and nerve fibers, which are in close proximity to one another and induce itch. The impaired barrier function associated with the itch-scratch cycle further augments this vicious cycle. Recent advances in our understanding of itch pathophysiology shed light on peripheral and central neural sensitization of nerve fibers that contribute significantly to itch in atopic dermatitis. Recently, several new mediators have been described as associated with itch in atopic dermatitis, including serine proteases, interleukin 31, and nerve growth factor. This review covers the peripheral and central mechanisms and mediators involved in pathogenesis of itch in atopic dermatitis

A novel topical formulation containing strontium chloride significantly reduces the intensity and duration of cowhage-induced itch

The aim of this double-blinded, vehicle-controlled study was to test the antipruritic efficacy of topical strontium to relieve a nonhistaminergic form of itch that would be clinically relevant for chronic pruritic diseases. Itch induced with cowhage is mediated by PAR2 receptors which are considered to play a major role in itch of atopic dermatitis and possibly other acute and chronic pruritic conditions. The topical strontium hydrogel formulation (TriCalm®) was tested in a head-to-head comparison with 2 common topical formulations marketed as antipruritics: hydrocortisone and diphenhydramine, for their ability to relieve cowhage-induced itch. Topically-applied strontium salts were previously found to be effective for reducing histamine-induced and IgE-mediated itch in humans. However, histamine is not considered the critical mediator in the majority of skin diseases presenting with chronic pruritus. The current study enrolled 32 healthy subjects in which itch was induced with cowhage before and after skin treatment with a gel containing 4% SrCl2, control vehicle, topical 1% hydrocortisone and topical 2% diphenhydramine. Strontium significantly reduced the peak intensity and duration of cowhage-induced itch when compared to the control itch curve, and was significantly superior to the other two over-the-counter antipruritic agents and its own vehicle in antipruritic effect. We hereby show that a 4% topical strontium formulation has a robust antipruritic effect, not only against histamine-mediated itch, but also for non-histaminergic pruritus induced via the PAR2 pathway, using cowhage

Time course of continuous itch intensity ratings (on a visual analog scale of 0 to 100 mm) in atopic dermatitis subjects, following itch induction with histamine, cowhage and their combination.

<p>A significant difference in time course and in the magnitude of response is observed between cowhage and histamine-induced itch (p<0.0001).</p

Thermal sensory and pain thresholds in the tongue and chin change with age, but are not altered in burning mouth syndrome

Burning mouth syndrome (BMS) is a chronic orofacial pain syndrome that occurs in middle-aged and postmenopausal women and poses a therapeutic challenge to dermatologists and dentists. It has been suggested previously that BMS is a small-fiber neuropathy. This study was designed to examine thermal sensory and pain thresholds in the oral mucosa and chin, both innervated by the trigeminal nerve, in patients with BMS, as well as in healthy controls. In addition, the study proposed to examine whether there are any differences in oral thermal and pain sensations between the advanced age group, where BMS is prevalent and a younger group. Thermal and pain thresholds of BMS patients did not differ significantly from those of healthy subjects. An increased threshold to thermal warmth and a decreased threshold for cold sensation for the tongue and chin were noted in the group over 50 years in comparison with younger subjects, indicating a decreased sensitivity to thermal stimuli. The group over 50 years of age displayed an increased sensitivity to cold pain and a decreased sensitivity to hot pain in the tongue (compared with the chin). BMS patients do not demonstrate alterations in thermal and pain detection, thus failing to support a true small nerve neuropathy in this condition

An image of cowhage spicules inserted into the skin by gentle rubbing, under polarizing light at 5× magnification.

<p>An image of cowhage spicules inserted into the skin by gentle rubbing, under polarizing light at 5× magnification.</p

Time course of continuous itch intensity ratings (on a visual analog scale of 0 to 100 mm) in healthy subjects, following itch induction with histamine, cowhage and their combination.

<p>A significant difference in time course and in the magnitude of response is apparent between cowhage and histamine-induced itch (p<0.0001).</p