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Itch and pain are common complaints of patients with burn injuries. This study aimed to describe the prevalence and predictors of itch and moderate to severe pain in the first 12 months following a burn injury, and determine the association between itch, moderate to severe pain, work-related outcomes, and health-related quality of life following a burn injury.
Learn More >Itch stimuli are detected by specialized primary afferents, which convey the signal to the spinal cord, but how itch transmission is regulated is still incompletely known. Here, we investigated the roles of the neuropeptide Y (NPY)/Y2 receptor system on scratch behavior. The inhibitory Y2 receptor is expressed on mouse primary afferents and intrathecal administration of the Y2 agonist peptide YY (PYY)3-36 reduced scratch episode frequency and duration induced by compound 48/80, an effect that could be reversed by intrathecal pre-administration of the Y2 antagonist BIIE0246. Also, scratch episode duration induced by histamine could be reduced by PYY3-36. In contrast, scratch behavior induced by α-methyl-5HT, SLIGRL, chloroquine, topical dust mite extract, or mechanical itch induced by von Frey filaments was unaffected by stimulation of Y2. Primary afferent neurons expressing the Npy2r gene were found to co-express itch-associated markers such as natriuretic peptide precursor b, oncostatin M receptor and interleukin (IL) 31 receptor A. Accordingly, intrathecal PYY3-36 reduced the scratch behavior induced by IL-31. Our findings imply that the NPY/Y2 system reduces histaminergic and IL-31-associated itch through presynaptic inhibition of a subpopulation of itch-associated primary afferents. SIGNIFICANCE STATEMENT: The spinal neuropeptide Y system dampens scratching behavior induced by histaminergic compounds and interleukin 31, a cytokine involved in atopic dermatitis, through interactions with the Y2 receptor. The Y2 receptor is expressed by primary afferent neurons that are rich in itch-associated neurotransmitters and receptors such as somatostatin, natriuretic peptide precursor b and interlekin 31 receptors.
Learn More >Systemic treatments for severe childhood atopic dermatitis have limited evidence and/or are unlicensed. Despite the efficacy of anti-IgE medication (omalizumab) in the treatment of atopy, no large randomized studies in childhood atopic dermatitis have been published.
Learn More >Spinal gastrin-releasing peptide receptor-expressing (GRPR) neurons play an essential role in itch signal processing. However, the circuit mechanisms underlying the modulation of spinal GRPR neurons by direct local and long-range inhibitory inputs remain elusive. Using viral tracing and electrophysiological approaches, we dissected the neural circuits underlying the inhibitory control of spinal GRPR neurons. We found that spinal galanin GABAergic neurons form inhibitory synapses with GRPR neurons in the spinal cord and play an important role in gating the GRPR neuron-dependent itch signaling pathway. Spinal GRPR neurons also receive inhibitory inputs from local neurons expressing neuronal nitric oxide synthase (nNOS). Moreover, spinal GRPR neurons are gated by strong inhibitory inputs from the rostral ventromedial medulla. Thus, both local and long-range inhibitory inputs could play important roles in gating itch processing in the spinal cord by directly modulating the activity of spinal GRPR neurons.
Learn More >Patients with chronic pruritus are in desperate need of novel treatment options, as current therapeutic possibilities are often not effective, have a poor level of evidence and are mostly off label. In recent years, much effort has been put into the identification of potential targets for the treatment of chronic pruritus. More importantly, a number of promising new drugs that are aimed at treating pruritus in different conditions are currently in advanced stages of clinical trials. Here, current pharmacological developments leading to potential new drugs for the treatment of chronic pruritus within various conditions are summarized. Hopefully, these new approaches will result in effective and safe therapies for our patients with chronic pruritus associated with dermatological or non-dermatological diseases in the near future. This article is protected by copyright. All rights reserved.
Learn More >Atopic dermatitis is associated with substantial patient and caregiver burden. Currently available treatments for atopic dermatitis are inadequate or contraindicated for some patients. Abrocitinib (PF-04965842) is an oral Janus kinase 1 selective inhibitor under investigation for the treatment of atopic dermatitis.
Learn More >Itch is a multidimensional experience involving various brain regions associated with sensory perception and emotion, as well as an urge to scratch employing the motor system. Scratch temporarily relieves itch sensation in healthy subjects. However, in patients with chronic itch, rather than inhibit, scratch may aggravate itch. Patients with chronic itch, such as those with atopic dermatitis, experience severe itch and a strong desire to scratch. This urge to scratch is the driving force underlying the formation of the itch scratch-cycle, an addictive and vicious cycle in chronic itch patients. This vicious itch-scratch behavior and various types of addiction (henceforth, including recreational drug use) were shown to share common sensory mechanisms. Abnormalities have been observed in central neural circuits, including the reward, motivation/drive, control, and learning/memory circuits, as well as other brain systems. Reward systems, including the ventral tegmental area (VTA), nucleus accumbens (NAc), and striatum, are important for brain processing of both addiction and itch. In addition to reward, addicted individuals can experience severe disruptions in motor control, cognitive awareness, executive function, learning/memory and even emotional functions. Findings showing that addiction and itch share a common neurobiological foundation could have important mechanistic and therapeutic implications. Here we propose that similar neuroadaptations exist in addiction and chronic itch patients. This article is protected by copyright. All rights reserved.
Learn More >Rodent primary sensory neurons are commonly used for studying itch and pain neurophysiology, but translation from rodents to larger mammals and humans is not direct and requires further validation to make correlations.
Learn More >We recently reported that swelling resulting from 2,4,6-trinitrochlorobenzene (TNCB) challenge might be associated with recruitment of neutrophils. However, it is not known whether neutrophil recruitment is affected by scratching at inflamed sites or not. Therefore, the effects of an Elizabethan collar on the TNCB-induced upregulation of ELR-positive chemokines (CXCL1, CXCL2, and CXCL5) and neutrophil recruitment were investigated. Mice were sensitized by the application of TNCB on abdominal skin. Then, the mice were challenged three times with TNCB to auricle of the ear. To prevent scratching at inflamed sites, an Elizabethan collar was placed on the mice from just before the first challenge until the end of the experiment. The effects of the Elizabethan collar on the TNCB-induced upregulation of CXCLs chemokines and recruitment of neutrophil were investigated. The increase of ear swelling by TNCB challenge was inhibited by the Elizabethan collar. TNCB-challenge-induced upregulation of TNF-α, IL-1β, IL-6, ELR chemokines, MPO, and ELA2 was also attenuated by the Elizabethan collar. The gene expression of CXCL1, CXCL2, and CXCL5 human homolog IL-8 was enhanced by TNF-α and IL-1β in human dermal fibroblasts and epidermal keratinocytes. We here suggest that scratching the site of inflammation leads to neutrophil accumulation mediated by TNF-α and IL-1β/ELR chemokines in TNCB-challenge-induced contact dermatitis in mice.
Learn More >Why do we have the sensation of itch and the associated scratching response? The conventional explanation is that arthropods and other environmental irritants elicit the sensation of itch that then leads to scratching and removal of the stimulus. This explanation is reasonable yet is too limiting for this fascinating sensory phenomenon and the associated somatic (voluntary) response of scratching. We delve into other explanations here. Some of these explanations fit within current areas of basic and clinical knowledge while others are speculative and may help to frame future discussions and study. This article is protected by copyright. All rights reserved.
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