Scratching the Five-Year ItchPublication of this editorial will mark the mid-point of my fifth (and final) year as Editor of the Journal of Investigative Dermatology (JID). This experience has met my expectations in many ways, and I am thankful to have been selected to be the JID’s Editor. However, there is a fair amount of work involved, and with experience, some of it has become routine. Against this background, it is delightful to have the opportunity to introduce a thematic section of the Journal that highlights a research area (itch) that features recent progress that is already clinically relevant.
Peripheral Mechanisms of ItchItch is a universally experienced sensation, and chronic itch can be as diabolically debilitating as pain. Recent advances have not only identified the neuronal itch sensing circuitry, but also have uncovered the intricate interactions between skin and immune cells that work together with neurons to identify itch-inducing irritants. In this review, we will summarize the fundamental mechanisms of acute itch detection in the skin, as well as highlight the recent discoveries relating to this topic.
A New Era with the Development of Cytokine-Based Therapy for PruritusPruritus is a common dermatological condition and negatively impacts QOL. Persistent pruritus and excessive scratching behavior can lead to the itch–scratch cycle that exacerbates inflammatory skin diseases. Conventional antipruritic drugs, such as antihistamines, corticosteroids, or anticonvulsants, are sometimes insufficient. Recently, however, molecularly targeted drugs, such as IL-31 or IL-4 receptor–targeting antibodies, have become available or are under clinical trials, dramatically changing the clinical situation.
The Sensation of Itch: From Biological Discovery to Medical TreatmentItch is an evolutionarily conserved sensation in vertebrates, and in its acute form, elicits a scratching reflex to expel environmental irritants such as insects, parasites, and toxins. However, in its chronic form, itch becomes highly debilitating and pathologic. Although originally considered a mild form of pain, the discovery of itch-specific molecular and cellular pathways in the last 15 years have greatly emboldened itch biology as a distinct field of inquiry (Wang and Kim, 2020). Furthermore, the unprecedented success of numerous therapeutics in this nascent field has drawn tremendous interest in solving the central symptom of itch across a number of medical disorders.
Interactions of the Neuro‒Immune‒Stromal Triad in ItchThis review focuses on recent advances in understanding the mechanisms involved in itch signaling in the skin and how these new findings fit into the wider picture of the expression of itch mediators and their receptors in the dermal layer. Because at present studies mostly concentrate on single cellular compartments (e.g., neural alone), we suggest that they may miss important interactions with other compartments. Therefore, to fully appreciate pruritus, we propose that studies should consider (e.g., using transcriptomic information) signal transmission within the entire neuro‒immune‒stromal triad.
Circuit Mechanisms of Itch in the BrainItch is an unpleasant somatic sensation with the desire to scratch, and it consists of sensory, affective, and motivational components. Acute itch serves as a critical protective mechanism because an itch-evoked scratching response will help to remove harmful substances invading the skin. Recently, exciting progress has been made in deciphering the mechanisms of itch at both the peripheral nervous system and the CNS levels. Key neuronal subtypes and circuits have been revealed for ascending transmission and the descending modulation of itch.