Activation of nociceptive fibers following skin injury triggers antiviral host defense immunity

Multiple innate immune signaling pathways become activated upon skin injury in order to reestablish the antimicrobial barrier and prevent infection. Damage to the skin barrier often elicits pain and/or itch, and leads to activation of the nervous system which communicates intimately with the immune system in a variety of skin inflammatory conditions (Kashem&Kaplan, 2016; Riol-Blanco et al. 2014, Chiu et al. 2013, Ding et al. 2016). Given that sensory dorsal root ganglion neurons express toll-like receptors that sense viral nucleic acids (Chiu et al.
Source: Journal of the American Academy of Dermatology - Category: Dermatology Source Type: research

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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
Publication date: Available online 11 April 2019Source: Brain, Behavior, and ImmunityAuthor(s): Haowu Jiang, Huan Cui, Tao Wang, Steven G. Shimada, Rui Sun, Zhiyong Tan, Chao Ma, Robert H. LaMotteAbstractSpontaneous itch and pain are the most common symptoms in various skin diseases, including allergic contact dermatitis (ACD). The chemokine (C-C motif) ligand 2 (CCL2, also referred to as monocyte chemoattractant protein 1 (MCP-1))and its receptor CCR2 are involved in the pathophysiology of ACD, but little is known of the role of CCL2/CCR2 for the itch- and pain-behaviors accompanying the murine model of this disorder, ter...
Source: Brain, Behavior, and Immunity - Category: Neurology Source Type: research
Abstract Spontaneous itch and pain are the most common symptoms in various skin diseases, including allergic contact dermatitis (ACD). The chemokine (C-C motif) ligand 2 (CCL2, also referred to as monocyte chemoattractant protein 1 (MCP-1))and its receptor CCR2 are involved in the pathophysiology of ACD, but little is known of the role of CCL2/CCR2 for the itch- and pain-behaviors accompanying the murine model of this disorder, termed contact hypersensitivity (CHS). C57BL/6 mice previously sensitized to the hapten, squaric acid dibutyl ester, applied to the abdomen were subsequently challenged twice with the hapte...
Source: Brain, Behavior, and Immunity - Category: Neurology Authors: Tags: Brain Behav Immun 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
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
Publication date: Available online 30 July 2018Source: BurnsAuthor(s): Vetrichevvel Palanivelu, Siaavash Maghami, Hilary J. Wallace, Dulharie Wijeratne, Fiona M. Wood, Mark W. FearAbstractBurn scars can be associated with significant loss of cutaneous sensation, paresthesia and chronic pain. Long-term systemic changes in cutaneous innervation may contribute to these symptoms and dorsal root ganglia have been implicated in the development of chronic neuropathic pain. Therefore we hypothesized that changes in cutaneous innervation after burn injury may be mediated at the level of the dorsal root ganglia. Burn group rats (n&n...
Source: Burns - Category: Dermatology Source Type: research
Abstract Loss-of-function mutations in the enzyme 7-dehydrocholesterol reductase are responsible for the Smith–Lemli–Opitz syndrome, in which 7-dehydrocholesterol (7-DHC) levels are markedly increased in the plasma and tissues of patients. This increase in 7-DHC is probably associated with the painful and itchy photosensitivity reported by the majority of patients with Smith–Lemli–Opitz syndrome. To identify the molecular targets involved in the activation and photosensitization of primary afferents by 7-DHC, we focused on TRPA1 and TRPV1, two ion channels expressed in nociceptive nerve endings an...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research
Abstract Chronic pain and itch are common hypersensitivity syndromes that are affected by endogenous mediators. We applied a systems-based, translational approach to predict, discover, and characterize mediators of pain and itch that are regulated by diet and inflammation. Profiling of tissue-specific precursor abundance and biosynthetic gene expression predicted that inflamed skin would be abundant in four previously unknown 11-hydroxy-epoxy- or 11-keto-epoxy-octadecenoate linoleic acid derivatives and four previously identified 9- or 13-hydroxy-epoxy- or 9- or 13-keto-epoxy-octadecenoate linoleic acid derivative...
Source: Science Signaling - Category: Biomedical Science Authors: Tags: Sci Signal Source Type: research
Chronic pain and itch are common hypersensitivity syndromes that are affected by endogenous mediators. We applied a systems-based, translational approach to predict, discover, and characterize mediators of pain and itch that are regulated by diet and inflammation. Profiling of tissue-specific precursor abundance and biosynthetic gene expression predicted that inflamed skin would be abundant in four previously unknown 11-hydroxy-epoxy- or 11-keto-epoxy-octadecenoate linoleic acid derivatives and four previously identified 9- or 13-hydroxy-epoxy- or 9- or 13-keto-epoxy-octadecenoate linoleic acid derivatives. All of these me...
Source: Signal Transduction Knowledge Environment - Category: Science Authors: Tags: STKE Research Articles Source Type: news
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
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