scholarly journals How Do Neurons Signal Itch?

2021 ◽  
Vol 8 ◽  
Author(s):  
Martin Schmelz
Keyword(s):  
Temporal Pattern ◽  
Treatment Options ◽  
Pattern Theory ◽  
Chronic Itch ◽  
Neurophysiological Studies ◽  
Itch Sensation ◽  
Current Experimental Data ◽  
Neuronal Specificity ◽  
Clinical Questions ◽  
Discharge Patterns

Mechanistic theories of itch are based on neuronal specificity, stimulus intensity, and temporal or spatial discharge patterns. Traditionally, these theories are conceptualized as mutually exclusive, assuming that finding evidence for one theory would exclude the others and could sufficiently explain itch. Current experimental data primarily support the specificity or pattern theory of itch. However, in contrast to an assumed inherent exclusivity, recent results have shown that even within itch-specific pathways in the spinal cord, temporal discharge patterns are important as sustained pruriceptor is required to allow successful transsynaptic signal progression. Also, optogenetic activation of pruriceptors suggest that the combination of neuronal specificity and temporal pattern determines the sensory effect: tonic activation of pruriceptors is required to induce scratching behavior whereas short-lasting stimulation rather causes withdrawal. In addition to the mere duration of discharge, also the temporal pattern or spatial aspects could critically contribute to elicit pruritus instead of pain. Basic neurophysiological studies trying to validate neuronal theories for pruritus in their pure form provide unitary concepts leading from neuronal discharge to the itch sensation. However, the crucial clinical questions have the opposite perspective: which mechanisms explain the chronic itch in a given patient or a given disease? In trying to solve these clinical problems we should not feel bound to the mutual exclusive nature of itch theories, but rather appreciate blending several theories and also accept combinations of itch and pain. Thus, blended versions of itch theories might better suffice for an explanation of chronic itch in patients and will improve the basis for mechanistic treatment options.

scholarly journals Breaking the Itch–Scratch Cycle: Topical Options for the Management of Chronic Cutaneous Itch in Atopic Dermatitis

Medicines ◽  
2019 ◽  
Vol 6 (3) ◽  
pp. 76 ◽  
Author(s):  
Ian P. Harrison ◽  
Fabrizio Spada
Keyword(s):  
Atopic Dermatitis ◽  
Treatment Options ◽  
Calcineurin Inhibitors ◽  
Cost Of Treatment ◽  
Topical Calcineurin Inhibitors ◽  
Chronic Itch ◽  
Itch Sensation ◽  
Chronic Pruritus

Chronic itch is an unpleasant sensation that triggers a desire to scratch that lasts for six weeks or more. It is a major diagnostic symptom of myriad diseases, including atopic dermatitis for which it is the most prominent feature. Chronic itch can be hugely debilitating for the sufferer, damaging in terms of both the monetary cost of treatment and its socioeconomic effects, and few treatment options exist that can adequately control it. Corticosteroids remain the first line treatment strategy for atopic dermatitis, but due to the risks associated with long-term use of corticosteroids, and the drawbacks of other topical options such as topical calcineurin inhibitors and capsaicin, topical options for itch management that are efficacious and can be used indefinitely are needed. In this review, we detail the pathophysiology of chronic pruritus, its key features, and the disease most commonly associated with it. We also assess the role of the skin and its components in maintaining a healthy barrier function, thus reducing dryness and the itch sensation. Lastly, we briefly detail examples of topical options for the management of chronic pruritus that can be used indefinitely, overcoming the risk associated with long-term use of corticosteroids.

scholarly journals Molecular signature of pruriceptive MrgprA3+ neurons

2019 ◽  
Author(s):  
Yanyan Xing ◽  
Junyu Chen ◽  
Henry Hilley ◽  
Haley Steele ◽  
Jingjing Yang ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Molecular Mechanisms ◽  
Molecular Signature ◽  
Neuronal Populations ◽  
Pathological Conditions ◽  
Chronic Itch ◽  
Itch Sensation ◽  
Profile Changes ◽  
Allergic Contact

ABSTRACTItch, initiated by the activation of sensory neurons, is frequently associated with dermatological or systemic diseases and significantly affects patient quality of life. MrgprA3+ sensory neurons have been identified as one of the major itch-sensing neuronal populations. Mounting evidence has demonstrated that peripheral pathological conditions induce physiological regulations of sensory neurons, which is critical for the maintenance of chronic itch sensation. However, the underlying molecular mechanisms are not clear. Here we performed RNA sequencing of genetically labeled MrgprA3+ neurons under both naïve and allergic contact dermatitis condition. Our results revealed the unique molecular signature of itch-sensing neurons and the distinct transcriptional profile changes that result in response to dermatitis. We found enrichment of nine Mrgpr family members and two histamine receptors in MrgprA3+ neurons, suggesting that MrgprA3+ neurons are the main, direct neuronal target for histamine and Mrgprs agonists. In addition, Ptpn6 and Pcdh12 were identified as novel and highly selective markers of MrgprA3+ neurons. We also discovered that MrgprA3+ neurons respond to skin dermatitis in a way that is unique from other sensory neurons by regulating a combination of transcriptional factors, ion channels, and key molecules involved in synaptic transmission. These results significantly increase our knowledge of itch transmission and uncover potentially novel targets for combating itch.

scholarly journals No significant relation of proinflammatory slanDCs with uremic pruritus

2020 ◽  
Vol 18 ◽  
pp. 205873922092685
Author(s):  
Christof Ulrich ◽  
Anja Leonhardt ◽  
Bogusz Trojanowicz ◽  
Eric Seibert ◽  
Roman Fiedler ◽  
...  
Keyword(s):  
Life Quality ◽  
Binary Logistic Regression ◽  
Monocyte Subset ◽  
Inclusion Criteria ◽  
Binary Logistic Regression Model ◽  
Uremic Pruritus ◽  
Chronic Itch ◽  
Itch Sensation ◽  
Study Inclusion

The pathogenesis of the pruritus associated with chronic kidney disease-(CKD-aP) is not completely understood. Endocrine, metabolic, neuropathic, and inflammatory disorders were suspected to be the origin of CKD-aP. Based on the hypothesis which suggests that deregulated systemic inflammation may play a crucial role in CKD-a, we investigated the potential relation of an inflammatory monocyte subset (slanDCs) with CKD-aP. Itch questionnaire, visual analogue scale (VAS)-scoring, and Dermatology Life Quality Index (DQLI) were applied for the characterization of itch sensation. VAS-scoring was re-evaluated after 6 months. Monocytes were flow-cytometrically categorized into classical, intermediate, and non-classical subsets. slanDCs are part of the non-classical monocyte subpopulation. Sixty-six hemodialysis patients (CKD5-D) were screened of whom 43 met the study inclusion criteria. In all, 46.5% of patients were scored pruritus-positive (CKD-aP+). CKD-aP severity level of patients was moderate at the start of the study (VAS 5.3 ± 2.5) and remained unchanged after 6 months (VAS: 5.2 ± 1.9, P < 0.757). Thirty percent of patients were affected with mild, 30.0% with moderate, and 35.0% with severe itchiness. In contrast to all other factors tested solely slanDC showed a weak correlation to VAS-score (r = 0.41, P = 0.07). slanDC frequencies between CKD5-D patients with and without itch sensation, however, were not significantly different. Endocrine problems appeared to influence CKD-aP. CKD-aP + patients had significantly higher L-thyroxin supplementation than CKD-aP- (50.0% vs 8.7%, P < 0.005). A binary logistic regression model confirmed the significance of L-thyroxin medication on chronic itch problems of our CKD5-D patients ( P < 0.007). There is no clear evidence that slanDCs are related to uremic pruritus. Therefore, other factors underlie the pathophysiology of CKD-aP.

scholarly journals Neutrophils promote CXCR3-dependent itch in the development of atopic dermatitis

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Carolyn M Walsh ◽  
Rose Z Hill ◽  
Jamie Schwendinger-Schreck ◽  
Jacques Deguine ◽  
Emily C Brock ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Sensory Neurons ◽  
Treatment Options ◽  
Cellular Interactions ◽  
Immune Systems ◽  
Chronic Itch ◽  
Enhanced Expression ◽  
Neutrophil Depletion ◽  
Induced Genes ◽  
Neuropathic Itch

Chronic itch remains a highly prevalent disorder with limited treatment options. Most chronic itch diseases are thought to be driven by both the nervous and immune systems, but the fundamental molecular and cellular interactions that trigger the development of itch and the acute-to-chronic itch transition remain unknown. Here, we show that skin-infiltrating neutrophils are key initiators of itch in atopic dermatitis, the most prevalent chronic itch disorder. Neutrophil depletion significantly attenuated itch-evoked scratching in a mouse model of atopic dermatitis. Neutrophils were also required for several key hallmarks of chronic itch, including skin hyperinnervation, enhanced expression of itch signaling molecules, and upregulation of inflammatory cytokines, activity-induced genes, and markers of neuropathic itch. Finally, we demonstrate that neutrophils are required for induction of CXCL10, a ligand of the CXCR3 receptor that promotes itch via activation of sensory neurons, and we find that that CXCR3 antagonism attenuates chronic itch.

scholarly journals Responses of Inferior Colliculus Neurons to Double Harmonic Tones

2007 ◽  
Vol 98 (6) ◽  
pp. 3171-3184 ◽  
Author(s):  
Donal G. Sinex ◽  
Hongzhe Li
Keyword(s):  
Inferior Colliculus ◽  
Auditory System ◽  
Temporal Pattern ◽  
Second Harmonic ◽  
Neural Mechanisms ◽  
Acoustic Properties ◽  
Discharge Pattern ◽  
The Difference ◽  
Discharge Patterns ◽  
Simultaneous Sounds

The auditory system can segregate sounds that overlap in time and frequency, if the sounds differ in acoustic properties such as fundamental frequency (f0). However, the neural mechanisms that underlie this ability are poorly understood. Responses of neurons in the inferior colliculus (IC) of the anesthetized chinchilla were measured. The stimuli were harmonic tones, presented alone (single harmonic tones) and in the presence of a second harmonic tone with a different f0 (double harmonic tones). Responses to single harmonic tones exhibited no stimulus-related temporal pattern, or in some cases, a simple envelope modulated at f0. Responses to double harmonic tones exhibited complex slowly modulated discharge patterns. The discharge pattern varied with the difference in f0 and with characteristic frequency. The discharge pattern also varied with the relative levels of the two tones; complex temporal patterns were observed when levels were equal, but as the level difference increased, the discharge pattern reverted to that associated with single harmonic tones. The results indicated that IC neurons convey information about simultaneous sounds in their temporal discharge patterns and that the patterns are produced by interactions between adjacent components in the spectrum. The representation is “low-resolution,” in that it does not convey information about single resolved components from either individual sound.

scholarly journals Neutrophils promote CXCR3-dependent itch in the development of atopic dermatitis

2019 ◽  
Author(s):  
Carolyn M. Walsh ◽  
Rose Z. Hill ◽  
Jamie Schwendinger-Schreck ◽  
Jacques Deguine ◽  
Emily C. Brock ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Sensory Neurons ◽  
Treatment Options ◽  
Cellular Interactions ◽  
Immune Systems ◽  
Chronic Itch ◽  
Enhanced Expression ◽  
Neutrophil Depletion ◽  
Induced Genes ◽  
Neuropathic Itch

AbstractChronic itch remains a highly prevalent disorder with limited treatment options. Most chronic itch diseases are thought to be driven by both the nervous and immune systems, but the fundamental molecular and cellular interactions that trigger the development of itch and the acute-to-chronic itch transition remain unknown. Here, we show that skin-infiltrating neutrophils are key initiators of itch in atopic dermatitis, the most prevalent chronic itch disorder. Neutrophil depletion significantly attenuated itch-evoked scratching in a mouse model of atopic dermatitis. Neutrophils were also required for several key hallmarks of chronic itch, including skin hyperinnervation, enhanced expression of itch signaling molecules, and upregulation of inflammatory cytokines, activity-induced genes, and markers of neuropathic itch. Finally, we demonstrate that neutrophils are required for induction of CXCL10, a ligand of the CXCR3 receptor that promotes itch via activation of sensory neurons, and we find that that CXCR3 antagonism attenuates chronic itch.

Pruritus

2014 ◽  
Author(s):  
Hong-Liang Tey ◽  
Gil Yosipovitch ◽  
Jeffrey D Bernhard
Keyword(s):  
Treatment Options ◽  
Clinical Signs ◽  
Calcineurin Inhibitors ◽  
Clinical Findings ◽  
Screening Tests ◽  
Topical Calcineurin Inhibitors ◽  
Chronic Itch ◽  
Chronic Pruritus ◽  
Systemic Therapies

Pruritus, or itch, can be defined as a sensation that elicits the desire to scratch. Normal physiologic "acute" itch occurs daily and can usually be abolished by scratching the affected area. On the other hand, chronic itch (defined as itch that persists for 6 weeks or more) is often made worse by scratching and is associated with significant morbidity. The focus of this chapter is on chronic pruritus. Discussion includes causes, clinical evaluation, investigation of, and treatment for chronic pruritus. Tables cover the etiologic classification of chronic pruritus, a morphologic approach to typically pruritic dermatoses and their classic distribution (with illustrative images), systemic diseases and associated clinical signs, localized pruritus and underlying neuropathy, screening tests for pruritus, further investigations following results of clinical findings and screening tests, general measures for patients managing pruritus, topical treatment, topical calcineurin inhibitors, systemic therapies, recommended stepwise treatment options, and phototherapy. Also included are a patient history checklist, an algorithm outlining the approach to chronic pruritus, and images depicting various forms of pruritus. This review contains 16 highly rendered figures (including table images), 13 tables, and 41 references.

scholarly journals Itch Signaling in the Nervous System

Physiology ◽  
2011 ◽  
Vol 26 (4) ◽  
pp. 286-292 ◽  
Author(s):  
Joseph Jeffry ◽  
Seungil Kim ◽  
Zhou-Feng Chen
Keyword(s):  
Molecular Mechanisms ◽  
Somatosensory System ◽  
Mouse Genetics ◽  
Molecular Signaling ◽  
C Fibers ◽  
Chronic Itch ◽  
Itch Sensation ◽  
Somatic Sensation ◽  
Psychophysical Studies ◽  
Important Progress

Itch is a major somatic sensation, along with pain, temperature, and touch, detected and relayed by the somatosensory system. Itch can be an acute sensation, associated with mosquito bite, or a chronic condition, like atopic dermatitis ( 29 , 59 ). The origins of the stimulus can be localized in the periphery or systemic, and associated with organ failure or cancer. Itch is also a perception originating in the brain. Itch is broadly characterized as either histamine-dependent (histaminergic) or histamine-independent (nonhistaminergic), both of which are relayed by subsets of C fibers and by the second-order neurons expressing gastrin-releasing peptide receptor (GRPR) and spinothalamic track (STT) neurons in the spinal cord of rodents. Historically, itch research has been primarily limited to clinical and psychophysical studies and to histamine-mediated mechanisms. In contrast, little is known about the signaling mechanisms underlying nonhistaminergic itch, despite the fact that the majority of chronic itch are mediated by nonhistaminergic mechanisms. During the past few years, important progress has been made in understanding the molecular signaling of itch, largely due to the introduction of mouse genetics. In this review, we examine some of the molecular mechanisms underlying itch sensation with an emphasis on recent studies in rodents.

Pruritus

2014 ◽  
Author(s):  
Hong-Liang Tey ◽  
Gil Yosipovitch ◽  
Jeffrey D Bernhard
Keyword(s):  
Treatment Options ◽  
Clinical Signs ◽  
Calcineurin Inhibitors ◽  
Clinical Findings ◽  
Screening Tests ◽  
Topical Calcineurin Inhibitors ◽  
Chronic Itch ◽  
Chronic Pruritus ◽  
Systemic Therapies

Pruritus, or itch, can be defined as a sensation that elicits the desire to scratch. Normal physiologic "acute" itch occurs daily and can usually be abolished by scratching the affected area. On the other hand, chronic itch (defined as itch that persists for 6 weeks or more) is often made worse by scratching and is associated with significant morbidity. The focus of this chapter is on chronic pruritus. Discussion includes causes, clinical evaluation, investigation of, and treatment for chronic pruritus. Tables cover the etiologic classification of chronic pruritus, a morphologic approach to typically pruritic dermatoses and their classic distribution (with illustrative images), systemic diseases and associated clinical signs, localized pruritus and underlying neuropathy, screening tests for pruritus, further investigations following results of clinical findings and screening tests, general measures for patients managing pruritus, topical treatment, topical calcineurin inhibitors, systemic therapies, recommended stepwise treatment options, and phototherapy. Also included are a patient history checklist, an algorithm outlining the approach to chronic pruritus, and images depicting various forms of pruritus. This review contains 16 highly rendered figures (including table images), 13 tables, and 41 references.

scholarly journals Counter-stimuli Inhibit GRPR Neurons via GABAergic Signaling in the Spinal Cord

2018 ◽  
Author(s):  
Rita Bardoni ◽  
Devin M. Barry ◽  
Hui Li ◽  
Kai-Feng Shen ◽  
Joseph Jeffry ◽  
...  
Keyword(s):  
Neural Mechanisms ◽  
Projection Neurons ◽  
List Type ◽  
Inhibitory Effects ◽  
Spinal Neurons ◽  
Chronic Itch ◽  
Spinal Mechanism ◽  
Itch Sensation ◽  
Neurokinin 1

AbstractA myriad of counter-stimuli, including algogens and cooling, could inhibit itch sensation; however, the underlying molecular and neural mechanisms remain poorly understood. Here, we show that the spinal neurons expressing gastrin releasing peptide receptor (GRPR) primarily comprise excitatory interneurons that receive direct and indirect inputs from C and Aδ fibers and form contacts with projection neurons expressing the neurokinin 1 receptor (NK1R). Optical or chemogenetic activation of GRPR neurons evokes itch behavior that is partly dependent on NK1R activation. Importantly, we show that noxious or cooling counter-stimuli inhibit the activity of GRPR neurons via GABAergic signaling. By contrast, capsaicin, which could evoke a mix of itch and pain sensations, could exert both excitatory and inhibitory effects on GRPR neurons. These data strengthen the role of GRPR neurons as a key circuit for itch transmission and illustrate a spinal mechanism whereby counter-stimuli inhibit itch by suppressing the function of GRPR neurons.HighlightsActivation of GRPR neurons evokes itch and is dependent upon NK1R activationGRPR neurons receive both direct and indirect inputs from C/Aδ fibersCounter-stimuli inhibit GRPR neurons via GABAergic signalingIncreased excitability of GRPR neurons in chronic itch condition

Sign in / Sign up

Export Citation Format

Share Document