A systematic review of questionnaires on itch by the Special Interest Group “Questionnaires” of the International Forum for the Study of Itch (IFSI) Introduction: Itch can be perceived differently across patients and it can affect daily life in various ways. It is essential to assess those aspects that are relevant for the individual patient’s needs to improve treatment of patients suffering from acute or chronic itch. The International Forum for the Study on Itch (IFSI) Special Interest Group on “Questionnaires” aims to propose tools to assess different dimensions of itch and improve patient care. As a first step, this study aimed at a systematically reviewing existing patients’ self-report questionnaires on itch. Materials and methods: The databases PubMed, PsycINFO, and CINAHL were systematically searched for any scientific publication describing patients’ self-report questionnaires that assess itch-related information (≥2 items). Information about the publication was extracted by 2 experts as well as which of the 14 predefined dimensions of itch (by the IFSI Special Interest Group) were assessed within the questionnaire, for instance, duration of itch, itch aggravating or relieving factors, and effects on quality of life. Results: From a total of 5282 records, 58 articles were derived describing 62 questionnaires. Over half of the questionnaires were developed for dermatological conditions, and the vast majority targeted at adults. Most questionnaires address itch-related disability and itch intensity. Affective qualities of itch, coping with itch, response to current itch treatment, and the opinion on the origin of itch are infrequently asked for. Discussion: The number and content of the items within a dimension vary greatly. Measurement properties of the questionnaires were not systematically addressed, as these were often not reported in the original publication. Future research should focus on selecting adequate and reliable (sub)scales to develop a modular questionnaire system in order to uniformly assess the individual patient’s demands and improve care.

Placebo and nocebo effects on itch: a review of experimental methods Itch is a commonly experienced symptom of acute and chronic dermatological and systemic conditions. Placebo and nocebo effects, positive and negative effects experienced after both real and sham interventions, putatively due to positive or negative outcome expectancies, can have a significant impact on the experience of itch and its treatment. Experimental methods to induce and study placebo and nocebo effects on itch have been developed, utilizing various combinations of expectancy-induction methods (eg, conditioning, verbal suggestions) and short-acting itch-evoking stimuli (eg, histamine, electrical, or mechanical stimulation). The aim of this review is to describe the current research methods used to induce placebo and nocebo effects on itch, and the results of these studies. The benefits and drawbacks of different expectancy-induction methods and itch-evoking stimuli are described, and future directions for research and clinical application are discussed.

Signs of chronic itch in the mouse imiquimod model of psoriasiform dermatitis: sex differences and roles of TRPV1 and TRPA1 Plaque psoriasis is a chronic inflammatory skin disease that affects a substantial proportion of the world population. This disorder is characterized by scaly, thick skin, intense ongoing itch, and itch from light touch (such as clothing contacting skin, called “alloknesis”). Imiquimod is a topical treatment for basal cell carcinomas and warts that has been used to create a mouse model of plaque psoriasis. Imiquimod-treated male, but not female, wildtype B6 mice showed significant increases in spontaneous scratching, while both sexes exhibited increased alloknesis, indicative of chronic itch. TRPV1 and TRPA1 knockout (KO) mice all exhibited numeric increases in spontaneous scratching which were significant for TRPV1KO mice and TRPA1KO males. Female TRPV1KO and TRPA1KO mice exhibited imiquimod-induced increases in alloknesis scores that did not significantly differ from wildtypes, while alloknesis scores in imiquimod-treated male TRPV1KO and TRPA1KO mice were significantly lower compared with wildtypes, suggesting that these ion channels are necessary for the development of alloknesis in males but not females in this model. Curiously, none of the groups exhibited any significant overall change in chloroquine-evoked scratching following imiquimod treatment, indicating that hyperknesis does not develop in this mouse model. Overall, the data indicate that there are sex differences in this mouse model of psoriasis, and that TRPV1 and TRPA1 ion channels have a small role in promoting the development of itch sensitization. This contrasts with the far greater role these channels play in the manifestation of skin changes in psoriatic dermatitis.

MrgprX1 mediates neuronal excitability and itch through tetrodotoxin-resistant sodium channels In this study, we sought to elucidate the molecular mechanism underlying human Mas-related G protein–coupled receptor X1 (MrgprX1)-mediated itch sensation. We found that activation of MrgprX1 by BAM8-22 triggered robust action potential discharges in dorsal root ganglion neurons. This neuronal excitability is not mediated by transient receptor potential (TRP) cation channels, M-type potassium channels, or chloride channels. Instead, activation of MrgprX1 lowers the activation threshold of tetrodotoxin-resistant sodium channels and induces inward sodium currents. These MrgprX1-elicited action potential discharges can be blocked by Pertussis toxin and a Gβγ inhibitor—Gallein. Behavioral results showed that Nav1.9 knockout but not TRPA1 knockout significantly reduced BAM8-22 evoked scratching behavior. Collectively, these data suggest that activation of MrgprX1 triggers itch sensation by increasing the activity of tetrodotoxin-resistant voltage-gated sodium channels.