A Test–Retest Reliability Study of Human Experimental Models of Histaminergic and Non-histaminergic Itch

Abstract

Numerous exploratory, proof-of-concept and interventional studies have used histaminergic and non-histaminergic human models of itch. However, no reliability studies for such surrogate models have been conducted. This study investigated the test-retest reliability for the response to histamine- and cowhage- (5, 15, 25 spiculae) induced itch in healthy volunteers. Cowhage spiculae were individually applied with tweezers and 1% histamine was applied with a skin prick test (SPT) lancet, both on the volar forearm. The intensity of itch was recorded on a visual analogue scale and self-reported area of itch was assessed 5 and 10 min after itch provocation. Reliability of the evoked itch (area under the curve and peak intensity) was assessed by the coefficient of variation (CV), intra-class correlation coefficient (ICC), and sample size estimation for parallel and cross-over designs. Cowhage (ICC = 0.57-0.77, CVbetween = 97%, CVwithin = 41%) and histamine: (ICC = 0.83-0.93, CVbetween = 97%, CVwithin = 20%) exhibited moderate-to-excellent intra-individual reliability and moderate inter-individual reliability for the itch intensity. For a test-retest observation period of one week, SPT-delivered histamine and application of cowhage-spiculae are reproducible human models of itch. The high inter-individual and low intra-individual variability suggests cross-over designed studies when applicable.

Antipruritic effect of pretreatment with topical capsaicin 8% on histamine- and cowhage-evoked itch in healthy volunteers: a randomized, vehicle-controlled, proof-of-concept trial

“…Each arm was allocated either histamine or cowhage, randomized by dominance. Histamine was applied by placing a small droplet in the centre of the pretreated area through which the epidermis was punctured with a skin prick test lancet (Allergopharma, Reinbek, Germany) mounted on a custom‐made 120‐g weighted pinprick stimulator (Aalborg University, Aalborg, Denmark) as previously outlined . The cowage spicules were counted using a stereomicroscope and placed in the centre of the treated area using tweezers.…”

Histaminergic and non‐histaminergic elicited itch is attenuated in capsaicin‐evoked areas of allodynia and hyperalgesia: A healthy volunteer study

“…The spicules were gently rubbed for 30-45 s in circular motion to facilitate epidermal penetration and removed with tape after termination of assessments. Both of these itch provocation methods have previously been found to be reliable (Andersen et al, 2017b).…”

Comparison of pruritus and sensory qualities induced by capsaicin, histamine and cowhage

“…3,[13][14][15][16][17][18] Two well-established experimental models of itch are skin provocation tests with histamine and cowhage. [19][20][21] Both mediators induce itch by activation of distinct receptors (H1R/H4R and PAR2/PAR4, respectively) located on distinct populations of cutaneous C-fibres. [22][23][24][25][26] Histamine-induced itch, expectedly, shares similarities with itch in urticaria, allergic reactions and mastocytosis, whereas cowhage-induced itch may share similarities with the itch in patients with atopic dermatitis.…”