Acta Dermato-Venereologica 99-2CompleteContent | Page 22

222 SHORT COMMUNICATION Assessing Punctate Administration of Beta-alanine as a Potential Human Model of Non-histaminergic Itch Janne D. CHRISTENSEN 1 , Silvia LO VECCHIO 1 , Jesper ELBERLING 2 , Lars ARENDT-NIELSEN 1 and Hjalte H. ANDERSEN 1 * 1 Laboratory for Experimental Cutaneous Pain and Itch Research, SMI ® , Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Fredrik Bajers Vej 7, Bld. A, A2-208, DK-9220 Aalborg, and 2 The Allergy Clinic, Department of Dermato-Allergology, Copenhagen University Hospital, Gentofte, Copenhagen, Denmark. *E-mail: [email protected] Accepted Oct 15, 2018; E-published Oct 15, 2018 features (no differences between any of the β-alanine Itch is a frequent symptom in many dermatological, syste- mic and neuropathic diseases (1). Several populations of conditions) (Fig. 1A–C). This was true both for the thin primary afferents respond to a variety of pruritogens mean and peak itch intensities and also independent of (2). In many diseases, such as atopic dermatitis (AD), the numbers of SPT lancet punctures conducted, i.e. 1 itch is thought to be transmitted non-histaminergically vs. 5 vs. 25 (Fig. 1D–F). Compared with both histamine (3). This fits the observation that antihistamines are inef- and cowhage, β-alanine induced significantly less robust fective in AD (4). For mechanistic studies, pharmaceu- itch. The temporal profiles of itch were different between tical proof-of-concept studies, and in relation to sensory cowhage and histamine, with cowhage exhibiting a more phenotyping of chronic itch patients, reliable provocation rapidly occurring peak and a faster decline than histamine. models of histamine-independent itch are important (5). The cowhage-model has become the “gold standard” of non- histaminergic evoked itch in humans (6, 7), and while it is a very effective model it suffers from several drawbacks: (i) carefully controlled applications of the spiculae are impossible, (ii) no com- mercial outlet supplies the spiculae, (iii), and batch-to-batch and inter-strain differences appear to be present. With this in mind, we aimed to develop a new and easily standardizable itch model re- lying on β-alanine, a naturally occurring amino acid. β-alanine evokes itch and a pricking sensation upon intradermal injection through activation of superfici- ally terminating mas-related G-protein- coupled receptor (Mrgpr) D-expressing neurones (8, 9). In non-human primates the primary afferent C-fibre population activated by β-alanine is distinct from that activated by histamine (10). The present study characterized the dose- response features of the β-alaninergic model of itch introduced with skin prick test (SPT) lancets in human skin. For comparative purposes itch provocations with cowhage and histamine were con- ducted and hyperknesis and cutaneous flare reactions were monitored. Fig. 1. (A) Temporal profile, (B) mean, and (C) peak itch intensities induced by different METHODS (see Appendix S1 ) 1 RESULTS β-alanine introduced with SPT lancets did not exhibit clear dose-response doi: 10.2340/00015555-3067 Acta Derm Venereol 2019; 99: 222–223 pruritogens. Cowhage and histamine induced significantly higher peak and mean itch than all other provocations. Temporal profile (D) as well as (E) mean and (F) peak itch intensities induced by 10% β-alanine when administered by 1, 5 or 25 skin punctures. No differences were observed. (G) Hyperknesis was present only following cowhage and histamine provocations. (H) Only histamine produced a robust axon-reflex-flare, while the 25 skin prick procedure caused (I) a small, but significant, flare reaction. NRS: numerical rating scale; SPT: skin prick test administration (i.e. number of punctures); VAS: visual analogue scale. Note: B, C and H as well as E, F and I share legends. *p  < 0.05, **p  < 0.01, #/## significant from all other conditions at p  < 0.05 or p  < 0.01, respectively. This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica.