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Switch to Itch—The many novel facets of pruritus research

Itch is one of the most important physiological senses in human beings and brings attention to the skin during transient or self-removable contact with plants or insects. Unfortunately, this sense is not resistant to permanent or constant stimulation, resulting in the persistent and annoying presence of chronic pruritus.[1] This phenomenon affects many patients, but did not receive much attention in the scientific community until the late 90s. The situation has since been reversed, now allowing for the definition and development of novel treatments for chronic pruritus based on our improved understanding of receptors, mediators and its mechanisms.[2‒5] This issue of Experimental Dermatology presents a comprehensive overview on different pathways and mechanisms of itch with special emphasis on presentation on novel ideas and concepts by leading experts in the field of itch. The skin is one hot spot for pruritus induction and maintenance, which is covered by several articles of this issue. Hashimoto and colleagues[6] (Miami, USA) covered the neglected but fascinating role of basophils in chronic itch and pruritic skin diseases, as well as the topographical differences of C nerve fibres and their implication in itch induction.[7] Nakashima and colleagues[8] (Kyoto, Japan) presented current knowledge on the interactions and communication of peripheral nerves and three immune cell subsets, mast cells, eosinophils and basophils, while Campion[9] (Dublin, Ireland) and colleagues demonstrated novel data on IL4 and IL13 and their role as pruritogens when injected intradermally. Talagas et al[10] (Brest, France) added their understanding of the crosstalk between keratinocytes and skin nerves; colleagues from the same centre, Huet and Misery[11], shed light on the mechanisms behind sensitive skin a common itchy problem when using cosmetics and toiletries namely that the epidermis represents a huge polymodal nociceptor. Feng and Hu[12] (St. Louis, USA) highlighted another type of cutaneous nerves: the mechanosensitive Merkel cell-neurite complex is involved in mechanisms underlying mechanical itch. Interestingly, Müller et al[13] (Basel, Switzerland) examined “good vibrations” and itch induction via this mechanical stimulus. They describe in detail how this framework can be used for studying mechanical itch. Beyond the skin, mechanisms of central processing and perception of itch are a hot area for current research reflected by several articles. The group of Müller[14] (Basel, Switzerland) released novel data on sex differences in the brain activation patterns of histamine-induced itch. More data on central mechanisms were introduced by Jones and colleagues[15] (Hull, UK). They demonstrated that a disruption of activity in the contralateral somatosensory cortex resulted in a reduced cortical processing of acute (histamine-induced) itch. Pavlenko and Akiyama[16] (Miami, USA) discussed the role of the amygdala in processing itch and the influence of chronic stress on it by inducing hyperexcitability in the amygdala. Ishiuji[17] (Tokyo, Japan) found that addiction and itch share some central neurobiological systems and neural circuits, including the reward, motivation/drive, control and learning/memory circuits. Also, some insights into the evolution of mechanisms of why we itch are thoughtfully discussed by EA Lerner[18] (Charlestown, USA) as well as the behavioural response of scratching and its learnability by Sanders et al[19] (Miami, USA). The clinical part start with novel definitions of chronic pruritus and chronic prurigo based on the extensive work led in Europe by a German group.[1,20] Murota and colleagues[21] (Nagasaki, Japan) covered the topic of why sweat aggravates itch of atopic dermatitis. Leon et al[22] (Miami, USA) describe several possible mechanisms why the scalp is so itchy in psoriasis. It is well known that psychological factors contribute to chronic pruritus and related scratching behaviour; these and other novel factors have been discussed by Evers and her team (Leiden, The Netherlands).[23] Several articles have focused on therapeutic options for chronic pruritus such as UV therapy and its effect on pruritus (F. Legat, Graz, Austria)[24], psychoactive drug use in pruritus (Reszke and Szepietowski,[25] Wroclaw, Poland), new treatment concepts in systemic itch (Kremer,[26] Erlangen, Germany), and the last article describes what is in the pipeline of therapeutic treatments for itch (Metz,[27] Berlin, Germany). We are hopeful that this special edition, which mainly focuses on viewpoints and hypothesis rather than studies, will provoke discussions and stimulate new thoughts among dermatologists and researchers alike that will further advance the field. We are aware that there are many aspects of itch in particular chronic itch that we did not cover but we hope that this special edition will serve as an eye opener to this evolving field. Last, but not least, we wish to dedicate this Focus Theme Issue to our mentors, Thomas A Luger, past Editor and now Honorary Editor of this journal, and Jeffrey D Bernhard, who we consider to be the pioneers of pruritus medicine.