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Itch and pain are important attention-demanding sensations that allow adaptive responses to potential bodily harm. An attentional bias towards itch and pain stimuli, i.e. preferential attention allocation towards itch- and pain-related information, has been found in healthy, as well as patient groups. However, it remains unclear whether attentional bias for itch and pain differs from a general bias towards negative information. Therefore, this study investigated attentional bias towards itch and pain in 70 itch- and pain-free individuals. In an attention task, itch- and pain-related stimuli, as well as negative stimuli, were presented alongside neutral stimuli. The results did not indicate an attentional bias towards itch-, pain-, and negative visual information. This finding suggests that people without itch and pain symptoms do not prioritize itch- and pain-related information above neutral information. Future research should investigate whether attention towards itch- and pain-related information might be biased in patients with chronic itch and pain.
Learn More >Chronic pruritus is a cardinal symptom of the inflammatory skin disease atopic dermatitis (AD). Pathogenic mechanisms in the periphery, spinal cord and the brain have been implicated in AD-related pruritus. Therefore, both systemic and topical administration of drugs could potentially provide relief. Despite efforts to elucidate the mechanisms behind AD-related pruritus and the relative contribution of peripheral nervous system and central nervous system (CNS), specific and successful treatment options have not yet been developed. Several small molecule drugs are currently being investigated to treat AD and AD-related pruritus. These small molecule drugs can be applied systemically but also topically, as they are able to penetrate into the skin due to their small size. Small molecule drugs specifically targeting peripheral itch transmission, e.g. peripherally selective κ-opioid receptors agonists and neurokinin 1 receptors antagonists, have so far been unable to improve AD-related pruritus when applied systemically, possibly because of the lack of CNS activity. Current evidence from clinical and preclinical trials with centrally acting or peripherally selective oral κ-opioid receptors agonists implies that CNS activity is required for an antipruritic effect. CNS activity is, however, directly associated with CNS-mediated side-effects. On the other hand, topical application of small molecules with anti-inflammatory activity such as Janus kinase inhibitors and phosphodiesterase 4 inhibitors, and also of κ-opioid receptor agonists, has shown promising results regarding their ability to reduce AD-related pruritus. In conclusion, topical application of anti-inflammatory compounds appears to be a highly promising strategy for the treatment of AD-related pruritus.
Learn More >Chronic pruritus, or itch lasting >6 weeks, is a common symptom and has a profoundly negative impact on quality of life. While many primary dermatologic disorders such as atopic dermatitis and chronic urticaria are characterized by pruritus, numerous other allergic, hepatobiliary, lymphoproliferative, neurologic, and renal disorders are associated with chronic pruritus. Itch involves complex interactions orchestrated by a variety of factors released from and acting on the skin, immune system, and the sensory nervous system. This review summarizes recent therapeutic developments for chronic pruritus with a focus on allergic and type 2 inflammatory pathways.
Learn More >Adult atopic dermatitis (AD) patients report skin pain, but the relationship with disease severity, anatomical location, and use of pain medication is unclear.
Learn More >Pruritus, a common symptom of psoriasis, negatively impacts quality of life; however, treatment of lesional skin does not consistently alleviate psoriatic itch.
Learn More >Atopic dermatitis (AD) is a highly prevalent, itchy inflammatory skin disorder that is thought to arise from a combination of defective skin barrier and immune dysregulation. Kallikreins (KLK), a family of serine proteases with a diverse array of homeostatic functions including skin desquamation and innate immunity, are speculated to contribute to AD pathogenesis. Their precise role in AD, however, has not been clearly defined. In this study, unbiased RNA-seq analyses identified KLK7 as the most abundant and differentially expressed KLK in both human AD and murine AD-like skin. Further, in mice, Klk7 expression was localized to the epidermis in both steady state and inflammation. However, KLK7 was dispensable for the development of AD-associated skin inflammation. Instead, KLK7 was selectively required for AD-associated chronic itch. Even without alleviation of skin inflammation, KLK7-deficient mice exhibited significantly attenuated scratching, compared to controls, after AD-like disease induction. Collectively, our findings indicate that KLK7 promotes AD-associated itch independently from skin inflammation, and reveal a previously unrecognized epidermal-neural mechanism of AD itch.
Learn More >Chronic pruritus causes major morbidity in epidermolysis bullosa (EB). The substance P-neurokinin 1 receptor (SP-NK1) pathway is a promising target for treating EB-related pruritus.
Learn More >Chronic itch can be a debilitating medical condition with clinical characteristics and impact akin to chronic pain. Itch severity is subjective and clinicians depend on patient reported numerical ratings scales (NRS); most commonly 24-hour worst itch (WI-NRS) has been validated including large scale studies. WI-NRS does not attempt to take into account itch duration or the variability that is often experienced throughout the day and night by chronic itch patients.
Learn More >Pruritus in atopic dermatitis has been studied extensively; however, evaluation of skin pain has been very limited. The aim of this study was to evaluate the presence, frequency and characteristics of skin pain in patients with atopic dermatitis. A survey was conducted of a representative sample of 5,000 18-80-year-old individuals selected from the French population according to sex, age, geographical area and socioprofessional status. Data on socio-demographic status and the presence of any skin disease were collected. Pain in the past month and health-related quality of life were evaluated. Average intensity of skin pain during the previous month was assessed with a horizontal visual analogue scale (0-10). Skin pain was reported by more than half of the patients with atopic dermatitis, at a pain intensity of almost 6/10. A neuropathic component was suggested by the Douleur Neuropathique – 4 questions (DN4) questionnaire (a tool for detection of neuropathic pain), as well as the presence of pain inside and outside of skin lesions. Severe alterations to health-related quality of life were assessed with the Dermatology Life Quality Index and Short Form 12 Health Survey (SF-12). Pain is reported frequently by patients with atopic dermatitis. Healthcare professionals should question patients about pain and provide effective treatments. Future clinical trials must take skin pain into account.
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