Enhanced scratching evoked by PAR-2 agonist and 5-HT but not histamine in a mouse model of chronic dry skin itch

Akiyama, Tasuku; Carstens, Mirela Iodi; Carstens, Earl

doi:10.1016/j.pain.2010.07.024

Cited by 110 publications

(129 citation statements)

References 35 publications

(45 reference statements)

Supporting

Mentioning

113

Contrasting

Unclassified

Order By: Relevance

“…Extension of these nerve fibers into the epidermis may contribute to spontaneous itch, aggravating itch responses and sensitization of itch signaling pathways (42). Enhanced animal behavioral scratching and DRG neuron responses to pruritogens have been documented in a mouse chronic dry-skin model (45). Similarly, CXCL10, which is a nonpruritogenic chemokine in naïve mice, was found to turn into a potent pruritogen in the inflamed skin of a mouse model of ACD (14).…”

Section: Discussionmentioning

confidence: 95%

IL-33/ST2 signaling excites sensory neurons and mediates itch response in a mouse model of poison ivy contact allergy

Liu

Tai

Achanta

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

212

195

View full text Add to dashboard Cite

Poison ivy-induced allergic contact dermatitis (ACD) is the most common environmental allergic condition in the United States. Case numbers of poison ivy ACD are increasing due to growing biomass and geographical expansion of poison ivy and increasing content of the allergen, urushiol, likely attributable to rising atmospheric CO 2 . Severe and treatment-resistant itch is the major complaint of affected patients. However, because of limited clinical data and poorly characterized models, the pruritic mechanisms in poison ivy ACD remain unknown. Here, we aim to identify the mechanisms of itch in a mouse model of poison ivy ACD by transcriptomics, neuronal imaging, and behavioral analysis. Using transcriptome microarray analysis, we identified IL-33 as a key cytokine up-regulated in the inflamed skin of urushiol-challenged mice. We further found that the IL-33 receptor, ST2, is expressed in small to medium-sized dorsal root ganglion (DRG) neurons, including neurons that innervate the skin. IL-33 induces Ca 2+ influx into a subset of DRG neurons through neuronal ST2. Neutralizing antibodies against IL-33 or ST2 reduced scratching behavior and skin inflammation in urushiol-challenged mice. Injection of IL-33 into urushiol-challenged skin rapidly exacerbated itch-related scratching via ST2, in a histamine-independent manner. Targeted silencing of neuronal ST2 expression by intrathecal ST2 siRNA delivery significantly attenuated pruritic responses caused by urushiol-induced ACD. These results indicate that IL-33/ST2 signaling is functionally present in primary sensory neurons and contributes to pruritus in poison ivy ACD. Blocking IL-33/ST2 signaling may represent a therapeutic approach to ameliorate itch and skin inflammation related to poison ivy ACD.A llergic contact dermatitis (ACD) is a common allergic skin condition caused by environmental or occupational allergens (1). In the United States, the most common cause of ACD is contact with poison ivy, which affects >10 million Americans per year (2, 3). Poison ivy ACD is also a serious occupational hazard, particularly among firefighters, forestry workers, and farmers, accounting for 10% of total U.S. Forest Services losttime injuries, and it often torments outdoor enthusiasts as well (3, 4). The major allergen in poison ivy is urushiol, contained in the oleoresinous sap of the plant and of related plants (e.g., poison oak and poison sumac) (5). An estimated 50-75% of Americans are sensitized to urushiol (6). Elevated atmospheric carbon dioxide and warming temperatures have increased the biomass of poison ivy and related plants, widened their geographic distribution, and increased plant urushiol content (7). These factors will likely increase allergenicity and result in even larger case numbers of poison ivy ACD in the future (8).The clinical manifestations of poison ivy-induced ACD are intense and persistent itch (pruritus), burning sensation, skin rashes, and swelling, followed by the appearance of vesicles in severe cases (2, 3, 9). Skin inflammation and pruritus ...

show abstract

Section: Discussionmentioning

confidence: 95%

IL-33/ST2 signaling excites sensory neurons and mediates itch response in a mouse model of poison ivy contact allergy

Liu

Tai

Achanta

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

212

195

View full text Add to dashboard Cite

show abstract

“…A range of mediators, such as histamine [3], prostaglandins [4], serotonin [5], bradykinin [6], cytokines [7], endothelin-1 [8], leukotrienes [9], proteases [10,11], neuropeptides [12] and opioids [13] orchestrate this response by acting on their receptors located on the nerve terminals. Pruritus (scratching behavior) is also a common symptom that results from insect bites, and can be experimentally induced in animals by the intradermal (i.d.)…”

Section: Introductionmentioning

confidence: 99%

Protective effects of exogenous and endogenous hydrogen sulfide in mast cell-mediated pruritus and cutaneous acute inflammation in mice

Rodrigues

Ekundi-Valentim

Florenzano

et al. 2017

Pharmacological Research

View full text Add to dashboard Cite

Protective effects of exogenous and endogenous hydrogen sulfide in mast cell-mediated pruritus and cutaneous acute inflammation in mice.Pharmacological Research http://dx.doi.org/10. 1016/j.phrs.2016.11.006 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Graphical abstract RESEARCH PAPER ABSTRACTThe recently described 'gasomediator' hydrogen sulfide (H2S) has been involved in pain mechanisms, but its effect on pruritus, a sensory modality that similarly to pain acts as a protective mechanism, is poorly known and controversial. The effects of the slowreleasing (GYY4137) and spontaneous H2S donors (Na2S and Lawesson's reagent, LR)were evaluated in histamine and compound 48/80 (C48/80)-dependent dorsal skin pruritus and inflammation in male BALB/c mice. Animals were intradermally (i.d.)injected with C48/80 (3 µg/site) or histamine (1 µmol/site) alone or co-injected with Na2S, LR or GYY4137 (within the 0.3 -100 nmol range). The involvement of endogenous H2S and KATP channel-dependent mechanism were also evaluated. Pruritus was assessed by the number of scratching bouts, whilst skin inflammation was evaluated by the extravascular accumulation of intravenously injected 125 I-albumin (plasma extravasation) and myeloperoxidase (MPO) activity (neutrophil recruitment). Histamine or C48/80 significantly evoked itching behavior paralleled by plasma extravasation and increased MPO activity. Na2S and LR significantly ameliorated histamine or C48/80-induced pruritus and inflammation, although these effects were less pronounced or absent with GYY4137. Inhibition of endogenous H2S synthesis exacerbated C48/80-induced responses, whereas the blockade of KATP channels by glibenclamide did not. Highperformance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) revealed that Na2S and LR, but not GYY4137, significantly attenuated C48/80-induced histamine release from rat peritoneal mast cell in vitro. We provide first evidences that H2S exerted protective effect against acute pruritus mediated via histaminergic pathways in murine skin, thus making of H2S donors a potential alternative/complementary therapy for treatment of acute pruritus.

show abstract

“…AD) with chronic pruritus are very often resistant to antihistamine therapies [54,55,60]. In a mouse dry skin model, histamine (in contrast of other itch inductors) did not stimulate scratching behavior [61], further supporting the hypothesis that histamine is not a central mediator of chronic pruritus.…”

Section: Histaminementioning

confidence: 82%

TRP Channels and Pruritus

Tóth¹,

Bı́ró²

2013

TOPAINJ

View full text Add to dashboard Cite

Itch (pruritus) is one of the most often seen sensory phenomena in clinical practice. Recent neurophysiological findings proposed the existence of a novel pruriceptive system which includes a multitude of pruritogenic (itch-inducing) peripheral mediators, itch-selective pruriceptors, sensory afferent networks, spinal cord neurons, and certain central nervous system regions. In this review, we first introduce major features of the pruriceptive system. We then focus on defining the roles of transient receptor potential (TRP) ion channels in skin-coupled itch and provide compelling evidence that certain thermosensitive TRP channels (especially TRPV1, TRPV3, TRPV4, and TRPA1) are indeed key players in pruritus pathogenesis. Finally, we propose TRP-centered future experimental directions towards the therapeutic targeting of TRP channels in the clinical management of itch.

show abstract

Enhanced scratching evoked by PAR-2 agonist and 5-HT but not histamine in a mouse model of chronic dry skin itch

Cited by 110 publications

References 35 publications

IL-33/ST2 signaling excites sensory neurons and mediates itch response in a mouse model of poison ivy contact allergy

IL-33/ST2 signaling excites sensory neurons and mediates itch response in a mouse model of poison ivy contact allergy

Protective effects of exogenous and endogenous hydrogen sulfide in mast cell-mediated pruritus and cutaneous acute inflammation in mice

TRP Channels and Pruritus

Contact Info

Product

Resources

About