Itch

Despite accumulating evidence in rodents, the functional role of neuromedin B (NMB) in regulating somatosensory systems in primate spinal cord is unknown. We aimed to compare the expression patterns of NMB and its receptor (NMBR) and the behavioral effects of intrathecal (i.t.) NMB with gastrin-releasing peptide (GRP) on itch or pain in non-human primates (NHPs). We used six adult rhesus monkeys. The mRNA or protein expressions of NMB, GRP, and their receptors were evaluated by quantitative reverse transcription polymerase chain reaction, immunohistochemistry, or in situ hybridization. We determined the behavioral effects of NMB or GRP via acute thermal nociception, capsaicin-induced thermal allodynia, and itch scratching response assays. NMB expression levels were greater than those of GRP in the dorsal root ganglia and spinal dorsal horn. Conversely, NMBR expression was significantly lower than GRP receptor (GRPR). I.t. NMB elicited only mild scratching responses, whereas GRP caused robust scratching responses. GRP- and NMB-elicited scratching responses were attenuated by GRPR (RC-3095) and NMBR (PD168368) antagonists, respectively. Moreover, i.t. NMB and GRP did not induce thermal hypersensitivity and GRPR and NMBR antagonists did not affect peripherally elicited thermal allodynia. Consistently, NMBR expression was low in both itch- and pain-responsive neurons in the spinal dorsal horn. Spinal NMB-NMBR system plays a minimal functional role in the neurotransmission of itch and pain in primates. Unlike the functional significance of the GRP-GRPR system in itch, drugs targeting the spinal NMB-NMBR system may not effectively alleviate non-NMBR-mediated itch.

Scalp dysesthesia is an abnormal sensation of the scalp in the absence of cutaneous disease. It is characterized by a burning and/or itching sensation and can be related to a variety of neurogenic or psychogenic causes. This condition is extremely bothersome and is also common- especially amongst the geriatric population, in women, in patients with diabetes mellitus and patients with psychiatric history. However, despite its prevalence in many populations, there is limited data about its causes and characteristics. Given its limited cutaneous manifestations it is also easily misdiagnosed and an underrecognized cause of scalp pruritus in the dermatological community. Therefore, education on scalp dysesthesia is paramount to helping physicians identify and provide appropriate treatment for these patients. This review focuses predominately on the neurogenic causes (with a brief review of psychogenic itch) of scalp dysesthesia and the therapeutics that have been found to be effective for this condition. Neurogenic causes of scalp dysesthesia occur with damage to the central or peripheral pathways of itch sensation, resulting in modification and heightened sensitivity of nerves that result in abnormal sensations in the absence of or out of proportion to external stimuli. A comprehensive review of etiologies is provided here, ranging from lesions to the central nervous system caused by cervical spine disease, trigeminal trophic syndrome, tumor, stroke, and multiple sclerosis, to small fiber neuropathies caused by diabetes, brow lifts, keloid and burn scarring. Recently, there have also been reports of scalp dysesthesias associated with post-infectious COVID-19. Treatment options tailored towards disease severity and different causes of disease will also be discussed. By elucidating the different mechanisms and therapeutic treatments of scalp dysesthesia, we hope to provide clinicians with the tools to identify and treat this condition as well as encourage further research into its etiologies and therapeutics.

Translational research has changed the understanding of atopic dermatitis (AD) pathogenesis beyond the basic mechanisms of immunology. The study in patients of rational therapies based on targeted therapies (biologicals) provides valuable information from the patient and provides lessons of clinical immunology on clinically relevant mechanism of AD pathogenesis. AD features such as skin barrier defect, skin dysbiosis, and pruritus share a common abnormal adaptive immune response process. Skin-homing CLA+CD4+ memory T-cells produce IL-4, IL-13, and IL-31 which are key mediators in AD pathogenesis. Lessons learned from AD show that translational immunology allows generating rational therapies for AD and learning its immunopathogenesis in the patient.

Cholestatic itch is a disabling symptom that may be secondary to liver or biliary diseases. Management of cholestatic pruritus is complex. A systematic review and meta-analysis on the efficacy of treatments for cholestatic pruritus were performed. PubMed and Cochrane Library were searched using the algorithm "(hepatitis OR cholestatic OR liver) AND (pruritus OR itch) AND (management OR treatment OR treatments)" for 1975-2019. Of the 2,264 articles identified, 93 were included in a systematic review and 15 in a meta-analysis (studies evaluating pruritus with a visual analogue scale). Some treatments act by reducing levels of pruritogens in the enterohepatic cycle, others modify the metabolism or secretion of these pruritogens, or act on pruritus pathways. A further possible treatment is albumin dialysis. However, due to many heterogeneities in the reviewed studies it is difficult to identify and recommend an optimum treatment. Only 15 studies were included in the meta-analysis, due to the small number of randomized studies using a visual analogue scale.