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Pruritus is a common disease symptom with a variety of etiologies known to reduce patient quality of life. We aimed to characterize the racial and gender differences in the presentation of pruritus for itch-related patient visits both within a single institution and nationally. Cross sectional study of patients ≥ 18 years old seen at Johns Hopkins Health System between 1/1/12 and 1/1/18. Results were compared to data from 2005-2011 from the National Ambulatory Medical Care Survey (NAMCS) and the National Health Ambulatory Medical Care Survey (NHAMCS). Our findings indicate that itch patients at JHHS ( = 18,753) were more likely to be black compared to white patients (37% vs. 19%, < 0.01) when compared to patients without itch-a trend also noted nationally based on data from NAMCS/NHAMCS (26% vs. 21%, = 0.05). Black itch patients are also more likely to be diagnosed with prurigo nodularis (OR 2.37, < 0.0001), lichen planus (OR 1.22, < 0.0001), and atopic dermatitis OR 1.51, < 0.0001). Female itch patients are more likely to be diagnosed with autoimmune (OR 1.66, < 0.0001) and psychiatric comorbidities (OR 1.2-1.8, < 0.0001) than male itch patients. When compared to black itch patients nationally, white itch patients were more likely to visit a dermatologist (29% vs. 18%, = 0.028). Our data can identify associated conditions and demographic differences but are unable to support a causal relationship. Black and female patients are more likely to present with pruritus, a symptom associated with comorbidities such as prurigo nodularis, lichen planus, atopic dermatitis, and psychiatric conditions.
Learn More >Limited research suggests commonalities between urologic chronic pelvic pain syndromes (UCPPS) and other non-urologic chronic overlapping pain conditions (COPCs) including fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome. The goal of this case-control study was to examine similarities and differences between UCPPS and these other COPCs.
Learn More >Increased high sensitivity C- reactive protein (hs-CRP) levels have been found in many earlier studies on migraine, and recently also in persons with migraine and insomnia. The aim of this study was to see whether these findings could be reproduced in a large-scale population-based study.
Learn More >Mas-related G-protein-coupled receptor X1 (MRGPRX1) is a human sensory neuron-specific receptor and has been actively investigated as a therapeutic target for the treatment of pain. By use of two HTS screening hit compounds, 4-(4-(benzyloxy)-3-methoxybenzylamino)benzimidamide () and 4-(2-(butylsulfonamido)-4-methylphenoxy)benzimidamide (), as molecular templates, a series of human MRGPRX1 agonists were synthesized and evaluated for their agonist activity using HEK293 cells stably transfected with human MrgprX1. Conversion of the benzamidine moiety into a 1-aminoisoquinoline moiety carried out in the later stage of structural optimization led to the discovery of a highly potent MRGPRX1 agonist, -(2-(1-aminoisoquinolin-6-yloxy)-4-methylphenyl)-2-methoxybenzenesulfonamide (), not only devoid of positively charged amidinium group but also with superior selectivity over opioid receptors. In mice, compound displayed favorable distribution to the spinal cord, the presumed site of action for the MRGPRX1-mediated analgesic effects.
Learn More >Mechanical itch is a desire to scratch due to light mechanical stimuli. In this issue of Neuron, Pan et al. (2019) identify a feedforward inhibition circuit in the spinal cord dorsal horn that processes mechanical itch as well as spontaneous itch.
Learn More >Itch is a distinct aversive sensation that elicits a strong urge to scratch. Despite recent advances in our understanding of the peripheral basis of itch, we know very little regarding how central neural circuits modulate acute and chronic itch processing. Here we establish the causal contributions of defined periaqueductal gray (PAG) neuronal populations in itch modulation in mice. Chemogenetic manipulations demonstrate bidirectional modulation of scratching by neurons in the PAG. Fiber photometry studies show that activity of GABAergic and glutamatergic neurons in the PAG is modulated in an opposing manner during chloroquine-evoked scratching. Furthermore, activation of PAG GABAergic neurons or inhibition of glutamatergic neurons resulted in attenuation of scratching in both acute and chronic pruritis. Surprisingly, PAG GABAergic neurons, but not glutamatergic neurons, may encode the aversive component of itch. Thus, the PAG represents a neuromodulatory hub that regulates both the sensory and affective aspects of acute and chronic itch.
Learn More >Lightly stroking the lips or gently poking some skin regions can evoke mechanical itch in healthy human subjects. Sensitization of mechanical itch and persistent spontaneous itch are intractable symptoms in chronic itch patients. However, the underlying neural circuits are not well defined. We identified a subpopulation of excitatory interneurons expressing Urocortin 3::Cre (Ucn3) in the dorsal spinal cord as a central node in the pathway that transmits acute mechanical itch and mechanical itch sensitization as well as persistent spontaneous itch under chronic itch conditions. This population receives peripheral inputs from Toll-like receptor 5-positive (TLR5) Aβ low-threshold mechanoreceptors and is directly innervated by inhibitory interneurons expressing neuropeptide Y::Cre (NPY) in the dorsal spinal cord. Reduced synaptic inhibition and increased intrinsic excitability of Ucn3 neurons lead to chronic itch sensitization. Our study sheds new light on the neural basis of chronic itch and unveils novel avenues for developing mechanism-specific therapeutic advancements.
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