The Challenge of Basic Itch Research.

The Challenge of Basic Itch Research. J Rehabil Med. 2020 Jan 07;100(2): Authors: Carstens E, Follansbee T, Iodi Carstens M Abstract Basic mechanisms and pathways of itch signaling are reviewed, with an emphasis on the progress to date as well as remaining challenges in translating current knowledge to the clinical treatment of chronic itch. Recent studies reveal 3 subsets of pruriceptive sensory neurons highly expressing itch-related genes. Their fibers project into the spinal cord to activate neurons expressing gastrin releasing peptide (GRP) and its receptor (GRPR), which connect to neurons that express the substance P (NK-1) receptor and project to the parabrachial nucleus and thalamus. Spinal inhibitory interneurons release GABA, glycine and dynorphin to modulate segmental itch transmission. However, near-ly all pruriceptive neurons also respond to algogens such as capsaicin. Alternative theories of itch-pain discrimination, such as intensity or spatial contrast, are based on the observation that focal stimulation of nociceptive nerve endings elicits itch while more wide-spread stimulation elicits pain. These findings cloud the issue of a labeled line for itch- a long-debated but currently unresolved challenge. In higher primates there is a dichotomy of histaminergic and non-histaminergic itch-signaling pathways which is less demarcated in rodents, suggesting species differences. A cardinal symptom of chronic itch is alloknesis, i.e., mechanical or t...
Source: Journal of Rehabilitation Medicine - Category: Rehabilitation Tags: J Rehabil Med Source Type: research

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Publication date: Available online 11 January 2020Source: NeuroscienceAuthor(s): Zhuo Huang, Xin Zhou, Jun Zhang, Chun-Lin Mai, Jie-Zhen Mai, Chong Liu, Hui Zhang, Xian-Guo LiuAbstractItch (pruritus), specifically chronic itch associated with disease conditions, significantly impairs the patient’s quality of life. At present, the mechanisms underlying this aversive experience are still unclear, and the effective treatment of itch is largely unmet. Here, we report that intragastrical administration of bulleyaconitine A (BLA), which has been used for treating chronic pain for 30 years in China, inhibited itch-like beha...
Source: Neuroscience - Category: Neuroscience Source Type: research
Abstract Basic mechanisms and pathways of itch signaling are reviewed, with an emphasis on the progress to date as well as remaining challenges in translating current knowledge to the clinical treatment of chronic itch. Recent studies reveal 3 subsets of pruriceptive sensory neurons highly expressing itch-related genes. Their fibers project into the spinal cord to activate neurons expressing gastrin releasing peptide (GRP) and its receptor (GRPR), which connect to neurons that express the substance P (NK-1) receptor and project to the parabrachial nucleus and thalamus. Spinal inhibitory interneurons release GABA, ...
Source: Acta Derm Venereol A... - Category: Dermatology Authors: Tags: Acta Derm Venereol Source Type: research
We examined the expression of TRPV1 in peripheral tissue and DRG neurons of CPIP model rats and we studied whether CPIP model could induce peripheral sensitization of TRPV1 channel and enhance DRG neuron excitability. Then we examined the therapeutic effects of locally applied TRPV1 specific antagonist AMG9810 on pain responses of CPIP model rats. Lastly, we explored the effects of AMG9810 on DRG neuron hyperexcitability and spinal glial activation induced by CPIP. Our results demonstrate that TRPV1 plays an important role in mediating the behavioral hypersensitivity of CPIP model rats via promoting peripheral nociceptor a...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusion and Future Directions G protein bias may either be affinity/potency-dominant or efficacy-dominant (Table 1). A potential concern is that, despite using the same cellular assays, variations in agonist potency were determined by different, or even the same labs, potentially due to differences in expression levels of the receptor and signaling proteins that occurred during cell passaging. For example the reported arrestin recruitment potency for U69,593 has been reported to be as low as 67.7 nM (Spetea et al., 2017) and as high as 410 nM (Dunn et al., 2018), similarly for U50,488 potency has ranged from 36 to 1000...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology 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
Publication date: 19 December 2018Source: Neuron, Volume 100, Issue 6Author(s): Gang Chen, Yu-Qiu Zhang, Yawar J. Qadri, Charles N. Serhan, Ru-Rong JiThe previous decade has seen a rapid increase in microglial studies on pain, with a unique focus on microgliosis in the spinal cord after nerve injury and neuropathic pain. Numerous signaling molecules are altered in microglia and contribute to the pathogenesis of pain. Here, we discuss how microglial signaling regulates spinal cord synaptic plasticity in acute and chronic pain conditions with different degrees and variations of microgliosis. We highlight that microglial medi...
Source: Neuron - Category: Neuroscience Source Type: research
Toll-like receptors (TLRs) are nucleic acid–sensing receptors and have been implicated in mediating pain and itch. Here we report that Tlr8–/– mice show normal itch behaviors, but have defects in neuropathic pain induced by spinal nerve ligation (SNL) in mice. SNL increased TLR8 expression in small-diameter IB4+ DRG neurons. Inhibition of TLR8 in the DRG attenuated SNL-induced pain hypersensitivity. Conversely, intrathecal or intradermal injection of TLR8 agonist, VTX-2337, induced TLR8-dependent pain hypersensitivity. Mechanistically, TLR8, localizing in the endosomes and lysosomes, mediated ERK activati...
Source: The Journal of Experimental Medicine - Category: Internal Medicine Authors: Tags: Neuroinflammation, Neuroscience Articles Source Type: research
In this study, we determined the role of the CXCL10-CXCR3 axis in NP using a well-established CCI model. CCI significantly induced mechanical allodynia and thermal hyperalgesia. Following the pain course, a significant increase of CXCL10 and CXCR3 in both dorsal root ganglion (DRG) neurons and spinal cord (SC) neurons was detected in rats. Furthermore, intrathecal injection of CXCR3 inhibitor AMG487 was found to attenuate pain hypersensitivity in a dose-dependent manner in CCI. The expression of p-ERK was also depressed after intrathecal injection of AMG487 associated with a significant laxation of hyperalgesia, which demo...
Source: Neuroscience Letters - Category: Neuroscience Source Type: research
If you have mesothelioma and you’ve already received standard-of-care therapies, you may be considering an immunotherapy clinical trial. If you’re considering this option, a free immunotherapy teleconference is a great place to learn more. CancerCare recently hosted two one-hour education workshops featuring panels of immunotherapy experts. Part I of the teleconference presented an overview of immunotherapy. Part II of the teleconference, which is available online for free, focused exclusively on immunotherapy side effects. Understanding these issues and the role each patient plays in managing their own side ef...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
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