GRP receptor and AMPA receptor cooperatively regulate itch-responsive neurons in the spinal dorsal horn.

In this study, we investigated the mechanisms for the activation of itch-responsive GRPR+ neurons in the spinal dorsal horn (SDH). GRPR+ neurons expressed the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) containing the GluR2 subunit. In mice, peripherally elicited histaminergic and non-histaminergic itch was prevented by intrathecal (i.t.) administration of the AMPAR antagonist NBQX, which was consistent with the fact that firing of GRPR+ neurons in SDH under histaminergic and non-histaminergic itch was completely blocked by NBQX, but not by the GRPR antagonist RC-3095. Because GRP+ neurons in SDH contain glutamate, we investigated the role of GRP+ (GRP+/Glu+) neurons in regulating itch. Chemogenetic inhibition of GRP+ neurons suppressed both histaminergic and non-histaminergic itch without affecting the mechanical pain threshold. In nonhuman primates, i.t. administration of NBQX also attenuated peripherally elicited itch without affecting the thermal pain threshold. In a mouse model of diphenylcyclopropenone (DCP)-induced contact dermatitis, GRP, GRPR, and AMPAR subunits were upregulated in SDH. DCP-induced itch was prevented by either silencing GRP+ neurons or ablation of GRPR+ neurons. Altogether, these findings demonstrate that GRP and glutamate cooperatively regulate GRPR+ AMPAR+ neurons in SDH, mediating itch sensation. GRP-GRPR and the glutamate-AMPAR system may play pivotal roles in the spinal transmission of itch in rodents and nonhuman...
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Neuropharmacology Source Type: research

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CONCLUSION: We have demonstrated that OMC exhibits advanced analgesic, antipruritic and anti-inflammatory effects when compared with OG and OMP in ACD mice by regulating inflammation, chemokines, immune mediators and inhibiting the mRNA expression of TRPA1 and TRPV1. OMC has no irritation to the intact and damaged skin of rabbits. PMID: 31654757 [PubMed - as supplied by publisher]
Source: European Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharm Sci Source Type: research
CONCLUSION: We identified important similarities and differences in the clinical characteristics of adults with psoriasis and AD; these should help clinicians to prioritize and improve patient management. PMID: 31630393 [PubMed - as supplied by publisher]
Source: The British Journal of Dermatology - Category: Dermatology Authors: Tags: Br J Dermatol Source Type: research
Erica S. Tarabadkar† and Michi M. Shinohara*† Division of Dermatology, University of Washington, Seattle, WA, United States Skin directed therapies (SDTs) serve important roles in the treatment of early stage cutaneous T-cell lymphoma (CTCL)/mycosis fungoides (MF), as well as managing symptoms and improving quality of life of all stages. There are now numerous options for topical therapies that demonstrate high response rates, particularly in early/limited MF. Phototherapy retains an important role in treating MF, with increasing data supporting efficacy and long-term safety of both UVB and PUVA as ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In this study we used HPLC and LC/MS analysis, combined with a BATMAN-TCM platform, for detailed HPLC fingerprint analysis and network pharmacology of QP, and investigated the anti-inflammatory and antipruritic activities of QP on ACD induced by squaric acid dibutylester (SADBE) in mice. The BATMAN-TCM analysis provided information of effector molecules of the main ingredients of QP, and possible chronic dermatitis-associated molecules and cell signaling pathways by QP. In ACD mice, QP treatment suppressed the scratching behavior induced by SADBE in a dose-dependent manner and inhibited the production of Th1/2 cytokines in...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
This article reviews the acute neural transmission of pain, pruritus, and nausea symptoms, which can begin in the periphery and/or viscera. The subsequent multiple pathways in the central nervous system that become involved in the processing of these symptoms are also discussed. The authors describe human brain imaging studies that have revealed consistent cortical and subcortical networks  activated by these symptoms, including sensory, limbic, and associative regions. In particular, the authors discuss information revealed by the studies regarding the primary somatosensory cortex, secondary somatosensory cortex, ant...
Source: Innovations in Clinical Neuroscience - Category: Neuroscience Authors: Tags: Current Issue Neurologic Systems and Symptoms Neurology Pain Review central processing nausea pruritus Source Type: research
Abstract: Itch is a protective sensation producing a desire to scratch. Pathologic itch can be a chronic symptom of illnesses such as uremia, cholestatic liver disease, neuropathies and dermatitis, however current therapeutic options are limited. Many types of cell surface receptors, including those present on cells in the skin, on sensory neurons and on neurons in the spinal cord, have been implicated in itch signaling. The role of G protein signaling in the regulation of pruriception is poorly understood. We identify here 2 G protein signaling components whose mutation impairs itch sensation. R7bp (a.k.a. Rgs7bp) is a pa...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research
AbstractRecent studies have shown that the chemokine receptor CXCR3 and its ligand CXCL10 in the dorsal root ganglion mediate itch in experimental allergic contact dermatitis (ACD). CXCR3 in the spinal cord also contributes to the maintenance of neuropathic pain. However, whether spinal CXCR3 is involved in acute or chronic itch remains unclear. Here, we report thatCxcr3−/− mice showed normal scratching in acute itch models but reduced scratching in chronic itch models of dry skin and ACD. In contrast, both formalin-induced acute pain and complete Freund ’s adjuvant-induced chronic inflammatory pain were ...
Source: Neuroscience Bulletin - Category: Neuroscience Source Type: research
Eczema, a constellation of conditions that makes a person’s skin dry, itchy, red and scaly, affects an estimated 30 million Americans. It can shame and isolate people who have it.  And right now, the disease is having a moment in the sun thanks to its major role in HBO’s “The Night Of,” a crime drama mini-series that features a character who is heavily defined by having eczema. Played by John Turturro, lawyer John Stone is a disrespected “bottom feeder” attorney who usually hangs around NYPD precincts waiting for easy cases. He catches the trial of a lifetime when he wins the trust ...
Source: Healthy Living - The Huffington Post - Category: Consumer Health News Source Type: news
SPECIAL FROM Varicose veins, a vascular disease that causes swollen, twisted veins, affect up to 35 percent of the American population. They are usually found in the legs, but can appear elsewhere on the body. Also known as venous insufficiency, varicose veins occur when damaged veins have trouble sending blood from the legs to the heart. There are a lot of myths out there about this condition. We talked to Kathleen Gibson, MD, vascular surgeon and vein specialist of Lake Washington Vascular, Bellevue, WA, to get the real deal: Myth #1: Varicose veins are harmless. Dr. Gibson: Varicose veins can be just a cosmetic iss...
Source: Healthy Living - The Huffington Post - Category: Consumer Health News Source Type: news
Diane is a baker, now rejecting consumption of wheat and grains. She has a terrific story to tell and photos that show how dramatic her appearance and life have changed in just 6 weeks: “I suffered from joint pain, headaches, painful and heavy menstrual cycles, IBS [irritable bowel syndrome], exhaustion, and heart palpitations. Just a few days after starting on your Wheat Belly lifestyle, after acquiring all your books, the health benefits were apparent. I bought your first Wheat Belly book when it first came out, but it sat on my bookshelf. In desperation and from feeling so poorly and feeling as though I was more l...
Source: Wheat Belly Blog - Category: Cardiology Authors: Tags: Wheat-elimination success stories gluten grains joint pain obesity rash Weight Loss Source Type: blogs
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