An Anterior Cingulate Cortex-to-Midbrain Projection Controls Chronic Itch in Mice / 神经科学通报·英文版

Itch is an unpleasant sensation that provokes the desire to scratch. While acute itch serves as a protective system to warn the body of external irritating agents, chronic itch is a debilitating but poorly-treated clinical disease leading to repetitive scratching and skin lesions. However, the neural mechanisms underlying the pathophysiology of chronic itch remain mysterious. Here, we identified a cell type-dependent role of the anterior cingulate cortex (ACC) in controlling chronic itch-related excessive scratching behaviors in mice. Moreover, we delineated a neural circuit originating from excitatory neurons of the ACC to the ventral tegmental area (VTA) that was critically involved in chronic itch. Furthermore, we demonstrate that the ACC→VTA circuit also selectively modulated histaminergic acute itch. Finally, the ACC neurons were shown to predominantly innervate the non-dopaminergic neurons of the VTA. Taken together, our findings uncover a cortex-midbrain circuit for chronic itch-evoked scratching behaviors and shed novel insights on therapeutic intervention.

Effect of quercetin and role of nitric oxide pathway in chloroquine-induced scratching

Abstract Nitric oxide (NO) is an abundant mediator which is demonstrated to be involved in pruritus. Assuming that the increased NO also mediates chloroquine-induced pruritus, which is a frequent complication seen in the chronic chloroquine treatment, the current study aimed to investigate the effect of quercetin and the role of NO in chloroquine-induced pruritus in C57BL/6 mice. Model was created with subcutaneous chloroquine (400µg/site) injection to the nape of the mice. Effect of quercetin and role of NO were investigated with administration of quercetin, and co-administration with L-NAME, 7-NI and L-arginine before chloroquine injection. Locomotor activity was assessed by activity cage and number of the scratching bouts after chloroquine injection was recorded for 30 minutes. Our results show that quercetin significantly reduced scratching bouts at the doses of 10, 20, 40 and 80 mg/kg. Locomotor activity was decreased at the 40 and 80 mg/kg doses of quercetin. Additionally, decrease of the number of scratching bouts by quercetin prevented by L-arginine treatment, while L-NAME and 7-NI enhanced the anti-pruritic effect of sub-effective doses of quercetin. Therefore, our study demonstrated that acute injection of quercetin significantly diminished chloroquine-induced scratching behavior, and this effect is partly mediated by inhibition of neuronal nitric oxide synthase enzyme.

Expression of interleukin-31 in hypertrophic scar from postoperative incision tissue / 中华医学美学美容杂志

Objective:To explore the interleukin-31 protein expression in the hypertrophic scar of incision tissue after surgery and its underlying pathological impact.Methods:From February 2022 to February 2023, three HS patients scar tissue (HS) and their normal skin tissue (Control, NS) were obtained. Two patients were female and one patient was male. The tissues were fixed in 4% formalin and embedded in paraffin. Haematoxylin-eosin (HE) stain and immunohistochemical stain were used to evaluate the epidermal thickness, myofibroblasts of dermis and the expression level of IL-31 between HS and NS.Results:The epidermis thickness was (303.88±46.03) μm in HS group, while (133.02±17.40) μm in NS group ( t=12.60, P<0.001). The expression level of IL-31 protein was measured by IRS score and positive cell density. The IRS score was 9.89±2.03 of the basal layer in HS group and was 4.33±1.66 of the basal layer in NS group. The positive cell density was 786 343.83±159 627.97 of the basal layer in HS group ( P<0.001) and was 555 457.61±128 097.21 of the basal layer in NS group ( P=0.014). In the dermis layer, the IRS score was 7.11±1.05 in HS group and was 4.33±0.71 in NS group, the positive cell density was 156 760.97±26 046.10 in HS group ( P<0.001) and was 49 576.01±52 369.33 in NS group ( P<0.001). In the dermis layer, the count of myofibroblasts was 120.44±15.75 in HS group while was 27.39±14.89 in NS group ( t=23.79, P<0.001). Conclusions:Our study demonstrates that both myofibroblast count and IL-31 protein expression level are notably increased in HS patients. The expression of IL-31 protein is prominent in the cytoplasm of myofibroblasts, basal cells, macrophages and mast cells which could implicate that IL-31 may be a potential therapeutic target to enhance the resolution of HS.

Investigation on the current situation and analysis of related influencing factors of xerosis in elderly inpatients / 中国实用护理杂志

Objective:To investigate the prevalence and influencing factors of xerosis in elderly inpatients, to provide basis for effective prevention and management of xerosis.Methods:Using the cross-sectional survey method and the self-designed survey table of the current situation of xerosis and prevention of the elderly, the incidence of xerosis in 1 028 patients hospitalized in Suqian Hospital Affiliated to Xuzhou Medical University, Suqian City Hospital of Traditional Chinese Medicine and Siyang County Hospital of Traditional Chinese Medicine was investigated, and the related factors were analyzed.Results:The incidence of xerofosis was 20.23%(208/1028); the incidence of xerosis was 20.23% (208/1 028), which was mainly found in the lower limbs, with the incidence of 53.37% (111/208), among which the incidence of mild xerosis was the most, with the incidence of 51.44% (107/208). The incidence rate of the elderly patients with xerosis between different age, qualifications, nutritional status, comorbidity, Braden score, drug use, main caregivers, departments, and daily skin care were statistically significant ( χ2 values were 6.91-35.71, all P<0.05). Binary logistic regression analysis showed that age, nutritional status, comorbidity status, Braden score and daily skin care were the independent influencing factors of skin dryness in elderly inpatients. Conclusions:There is a common skin symptom of xerosis in the elderly. It is necessary to establish a standardized management process and take targeted preventive and nursing measures.

Acupuncture attenuates comorbid anxiety- and depressive-like behaviors of atopic dermatitis through modulating neuroadaptation in the brain reward circuit in mice

Atopic dermatitis (AD) is highly comorbid with negative emotions such as anxiety and depression. Although acupuncture has demonstrated efficacy in AD, its influence on comorbid anxiety and depression remains unclear. We sought to explore the impact and mechanisms of action of acupuncture on comorbid anxiety and depression of AD. AD-like skin lesions were induced by the topical application of MC903 to the mouse cheek. Acupuncture was performed at Gok-Ji (LI11) acupoints. AD-like phenotypes were quantified by lesion scores, scratching behavior, and histopathological changes. The effects of acupuncture on comorbid anxiety and depression-like behaviors were assessed using the elevated plus-maze (EPM), open-field tests (OFT), and tail-suspension test (TST). In addition, biochemical changes in the brain reward regions were investigated by immunoblotting for the expression of tyrosine hydroxylase (TH), dopamine D1 receptor (D1R), phospho-dopamine and cAMP-regulated phosphoprotein-32 kDa (pDARPP-32), phospho-cAMP response element binding protein (pCREB), ΔFosB, and brain-derived neurotrophic factor (BDNF) in the nucleus accumbens, dorsolateral striatum, and ventral tegmental area. Acupuncture effectively improved the chronic itching and robust AD-like skin lesions with epidermal thickening. Additionally, it considerably reduced comorbid anxiety- and depression-like symptoms, as indicated by more time spent in the open arms of the EPM and in the center of the open field and less time spent immobile in the TST. Higher pCREB, ΔFosB, BDNF, and pDARPP-32 levels, and reduced TH and D1R protein expression in the brain reward regions of AD mice were reversed by acupuncture treatment. The beneficial effects of acupuncture on clinical symptoms (scratching behavior) and comorbid psychological distress in AD strongly correlated with dorsal striatal ΔFosB levels. Collectively, these data indicate that acupuncture had a significant, positive impact on comorbid anxiety- and depression-like behaviors by modulating neuroadaptation in the brain reward circuit in mice with AD, providing a novel perspective for the non-pharmacological management of psychiatric comorbidities of AD.

Mitochondrial Reactive Oxygen Species Elicit Acute and Chronic Itch via Transient Receptor Potential Canonical 3 Activation in Mice / 神经科学通报·英文版

Mitochondrial reactive oxygen species (mROS) that are overproduced by mitochondrial dysfunction are linked to pathological conditions including sensory abnormalities. Here, we explored whether mROS overproduction induces itch through transient receptor potential canonical 3 (TRPC3), which is sensitive to ROS. Intradermal injection of antimycin A (AA), a selective inhibitor of mitochondrial electron transport chain complex III for mROS overproduction, produced robust scratching behavior in naïve mice, which was suppressed by MitoTEMPO, a mitochondria-selective ROS scavenger, and Pyr10, a TRPC3-specific blocker, but not by blockers of TRPA1 or TRPV1. AA activated subsets of trigeminal ganglion neurons and also induced inward currents, which were blocked by MitoTEMPO and Pyr10. Besides, dry skin-induced chronic scratching was relieved by MitoTEMPO and Pyr10, and also by resveratrol, an antioxidant. Taken together, our results suggest that mROS elicit itch through TRPC3, which may underlie chronic itch, representing a potential therapeutic target for chronic itch.

Newly diagnosed type II diabetes mellitus presenting with localized itch

Type II diabetes is caused by insulin resistance resulting in high blood sugar levels. Although the typical symptoms of diabetes are described as polyuria, polydipsia and fatigue as many as 60% of newly diagnosed patients with type II diabetes are asymptomatic. Here authors present a case of a 39-year-old male patient who presented with localized pruritus affecting the medial aspects of his forearms and upper legs as the sole symptom of newly diagnosed type II diabetes mellitus. The itch symptom markedly improved on significantly reducing his dietary intake of sugars and with the use of metformin. Authors hope to alert clinicians to consider the possibility of underlying diabetes in such presentations to enable swift diagnosis and consequent treatment. It is unusual to find patients presenting with localized itch without any corresponding cutaneous manifestations as a presentation of type II diabetes.

Medicinal plants as a source of future anti-pruritic drugs: a comprehensive review / Las plantas medicinales como fuente de futuros fármacos antipruríticos: una revisión exhaustiva

Pruritus is a distressing sensation of the skin that provokes the desire to scratch. Medicinal plants have been proposed as a worthful source for identifying new bioactive molecules. The aim of this study was to evaluate some medicinal plants and their phytochemicals used in the management of pruritus. Medicinal plants including Avena sativa, Borago officinalis, Capsicum frutescens, Curcuma longa, Fumaria spp., Mentha x piperita and Oenothera biennis showed the promising anti-pruritic activity in human studies. In experimental studies, Angelica sinensis, Betula platyphylla, Matricaria chamomilla, Rumex Japonicus, Saururus chinensis and Vaccinium myrtillus are among the best medicinal plants for management of pruritus. Essential oils, alkaloids, saponins, sterols, terpens, phenolic compounds, and fatty acids were the bioactive constituents of herbs which exhibited their anti-pruritic activity through different mechanisms. The most predominant mechanisms involved in activity of plant-derived molecules in pruritis include reducing serum IgE and proinflammatory cytokines, stabilizing mast cells, suppressing the Th2 cellular response, suppressing the expression of substance P and NF- κB, inhibiting prostaglandin E2 production, and activating receptors involved in itch sensation. Overall, several medicinal plants and its bioactive compounds have shown marked activity in the management of pruritus and therefore can be considered as an alternative source of treatment.

El prurito es una sensación molesta en la piel que provoca el deseo de rascarse. Las plantas medicinales han sido propuestas como una fuente valiosa para identificar nuevas moléculas bioactivas. El objetivo de este estudio fue evaluar algunas plantas medicinales y sus fitoquímicos en el manejo del prurito. Plantas medicinales que incluyen Avena sativa, Borago officinalis, Capsicum frutescens, Curcuma longa, Fumaria spp., Mentha x piperita y Oenothera biennis mostraron una prometedora actividad antiprurítica en estudios humanos. En estudios experimentales, Angelica sinensis, Betula platyphylla, Matricaria chamomilla, Rumex Japonicus, Saururus chinensis y Vaccinium myrtillus se encuentran entre las mejores plantas medicinales para el manejo del prurito. Los aceites esenciales, alcaloides, saponinas, esteroles, terpenos, compuestos fenólicos y ácidos grasos fueron los constituyentes bioactivos de las hierbas que mostraron actividad antiprurítica a través de diferentes mecanismos. Los mecanismos más predominantes implicados en la actividad de las moléculas derivadas de plantas en el prurito incluyen la reducción de la IgE sérica y las citoquinas proinflamatorias, la estabilización de los mastocitos, la supresión de la respuesta celular Th2, la supresión de la expresión de la sustancia P y NF-κB, la inhibición de la producción de prostaglandina E2 y la activación de receptores implicados en la sensación de picazón. En general, varias plantas medicinales y sus compuestos bioactivos han mostrado una actividad efectiva en el manejo del prurito y, por lo tanto, pueden ser consideradas como una fuente alternativa para su tratamiento.

Machine-Learning Based Automatic and Real-time Detection of Mouse Scratching Behaviors

Scratching is a main behavioral response accompanied by acute and chronic itch conditions, and has been quantified as an objective correlate to assess itch in studies using laboratory animals. Scratching has been counted mostly by human annotators, which is a time-consuming and laborious process. It has been attempted to develop automated scoring methods using various strategies, but they often require specialized equipment, costly software, or implantation of device which may disturb animal behaviors. To complement limitations of those methods, we have adapted machine learning-based strategy to develop a novel automated and real-time method detecting mouse scratching from experimental movies captured using monochrome cameras such as a webcam. Scratching is identified by characteristic changes in pixels, body position, and body size by frame as well as the size of body. To build a training model, a novel two-step J48 decision tree-inducing algorithm along with a C4.5 post-pruning algorithm was applied to three 30-min video recordings in which a mouse exhibits scratching following an intradermal injection of a pruritogen, and the resultant frames were then used for the next round of training. The trained method exhibited, on average, a sensitivity and specificity of 95.19% and 92.96%, respectively, in a performance test with five new recordings. This result suggests that it can be used as a non-invasive, automated and objective tool to measure mouse scratching from video recordings captured in general experimental settings, permitting rapid and accurate analysis of scratching for preclinical studies and high throughput drug screening.

Immune regulation by protein ubiquitination: roles of the E3 ligases VHL and Itch

Protein ubiquitination is an important means of post-translational modification which plays an essential role in the regulation of various aspects of leukocyte development and function. The specificity of ubiquitin tagging to a protein substrate is determined by E3 ubiquitin ligases via defined E3-substrate interactions. In this review, we will focus on two E3 ligases, VHL and Itch, to discuss the latest progress in understanding their roles in the differentiation and function of CD4 T helper cell subsets, the stability of regulatory T cells, effector function of CD8 T cells, as well as the development and maturation of innate lymphoid cells. The biological implications of these E3 ubiquitin ligases will be highlighted in the context of normal and dysregulated immune responses including the control of homeostasis, inflammation, auto-immune responses and anti-tumor immunity. Further elucidation of the ubiquitin system in immune cells will help in the design of new therapeutic interventions for human immunological diseases and cancer.

Intradermal administration of formalin to the cheek induces itch as well as pain behaviors in rats / 上海交通大学学报（医学版）

Objective· Formalin is a classic and most widely used algogenic substance,but its itchy effect is not clear.The present study aims to explore the hypothesis that formalin may induce itch as well as pain.Methods· Flinching,as well as licking and forelimb wiping of the site of injection were counted as pain responses,whereas biting and hind paw scratching of the cheek were counted as itchy responses.To discriminate formalin-induced sensations in rats,the irritant (saline as control) was injected,and then pain and itchy responses were recorded.Results · Intraplantar injection of formalin elicited biphasic behavior responses characterized as flinching,as well as biting or licking of the hind paw without significant gender differences.Following intradermal administration of formalin to the cheek,rats exhibited episodic forelimb wiping of the cheek,representative of pain.No gender difference was noticed for this type of behavior.In addition,episodes of hind paw scratches of the cheek,representative of pruritoceptive responses,also occurred.Interestingly,hind paw scratches appeared to be more pronounced in male than in female rats.Conclusion · Intradermal administration of formalin elicits pruritoceptive as well as nociceptive responses in rats.

Silencing Itch gene expression by ultrasound-targeted microbubble destruction to enhance the immune killing efficiency of T lymphocyte against lung neoplasms cells LA795 / 基础医学与临床

Objective To silence the expression of Itch gene of T-lymphocytes by ultrasound-targeted microbubble destruction (UTMD) and to investigate the cytotoxicity of transfected T lymphocytes against LA795 lung neoplasms cells in vitro. Methods T lymphocyte were isolated by magnetic bead,and an targeted shRNA to silence Itch gene of T lymphocytes was established.48 hours after transfection by UTMD,the transfection efficiency was detected and analyzed by fluorescence microscopy and flow cytometry;the expression of Itch protein was measured with Western blot;72 hours after transfection,the secretion of IL-2 and IFN-γ in the cell supernatant was measured by enzyme-linked immunosorbent assay (ELISA). The cytotoxicity activity changes against LA795 lung neoplasms cells was compared between transfected T lymphocytes and negative control or simplex T lymphocytes in vitro. Results The transfection rate to silence Itch gene of T lymphocytes by UTMD was 52.3%±3.8%. At 48 h after transfection,the Itch gene expression can be effectively suppressed by UTMD. Seventy-two hours after transfection,the secretion level of cytokines including IL-2 and IFN-γ,was significantly increased in the group of targeted shRNA to silence Itch gene of T lymphocytes by UTMD(P<0.05) and transfected T lymphocyte also showed more efficient killing ability against LA795 lung neoplasms cells than negative control or blank group at E : T of 10 : 1,20 : 1 and 40 : 1 (P<0.05). Conclusions Silencing the expression of Itch by UTMD can significantly promote immune activity of T lymphocyte,enhance the cytotoxicity activity of T lymphocyte against LA795 lung neoplasms cells in vitro.

Altered Expression of Differential Genes in Thoracic Spinal Cord Involved in Experimental Cholestatic Itch Mouse Model / 华中科技大学学报（医学）（英德文版）

The spinal origin of cholestatic itch in experimental obstructive jaundice mouse model remains poorly understood.In this study,the jaundice model was established by bile duct ligation (BDL) in mice,and differential gene expression patterns were analyzed in the lower thoracic spinal cord involved in cholestatic pruritus after BDL operation using high-throughput RNA sequencing.At 21st day after BDL,the expression levels of ENSRNOG00000060523,ENSRNOG00000058405 and ENSRNOG00000055193 mRNA were significantly up-regulated,and those of ENSRNOG00000042197,ENSRNOG00000008478,ENSRNOG00000019607,ENSRNOG00000020647,ENSRNOG00000046289,Gemin8,Serpina3n and Trim63 mRNA were significantly down-regulated in BDL group.The RNAseq data of selected mRNAs were validated by RT-qPCR.The expression levels of ENSRNOG00000042197,ENSRNOG00000008478,ENSRNOG00000019607,ENSRNOG00000020647,ENSRNOG00000046289 and Serpina3n mRNA were significantly down-regulated in BDL group.This study suggested that cholestatic pruritus in experimental obstructive jaundice mouse model is related with in the changes of gene expression profiles in spinal cord.

Altered Expression of Differential Genes in Thoracic Spinal Cord Involved in Experimental Cholestatic Itch Mouse Model / 华中科技大学学报（医学）（英德文版）

The spinal origin of cholestatic itch in experimental obstructive jaundice mouse model remains poorly understood.In this study,the jaundice model was established by bile duct ligation (BDL) in mice,and differential gene expression patterns were analyzed in the lower thoracic spinal cord involved in cholestatic pruritus after BDL operation using high-throughput RNA sequencing.At 21st day after BDL,the expression levels of ENSRNOG00000060523,ENSRNOG00000058405 and ENSRNOG00000055193 mRNA were significantly up-regulated,and those of ENSRNOG00000042197,ENSRNOG00000008478,ENSRNOG00000019607,ENSRNOG00000020647,ENSRNOG00000046289,Gemin8,Serpina3n and Trim63 mRNA were significantly down-regulated in BDL group.The RNAseq data of selected mRNAs were validated by RT-qPCR.The expression levels of ENSRNOG00000042197,ENSRNOG00000008478,ENSRNOG00000019607,ENSRNOG00000020647,ENSRNOG00000046289 and Serpina3n mRNA were significantly down-regulated in BDL group.This study suggested that cholestatic pruritus in experimental obstructive jaundice mouse model is related with in the changes of gene expression profiles in spinal cord.

Infection, Pain, and Itch / 神经科学通报·英文版

Pain and itch are unpleasant sensations that often accompany infections caused by viral, bacterial, parasitic, and fungal pathogens. Recent studies show that sensory neurons are able to directly detect pathogens to mediate pain and itch. Nociceptor and pruriceptor neurons respond to pathogen-associated molecular patterns, including Toll-like receptor ligands, N-formyl peptides, and bacterial toxins. Other pathogens are able to silence neuronal activity to produce analgesia during infection. Pain and itch could lead to neuronal modulation of the immune system or behavioral avoidance of future pathogen exposure. Conversely, pathogens could modulate neuronal signaling to potentiate their pathogenesis and facilitate their spread to other hosts. Defining how pathogens modulate pain and itch has critical implications for sensory neurobiology and our understanding of host-microbe interactions.

TNF-α/TNFR1 Signaling is Required for the Full Expression of Acute and Chronic Itch in Mice via Peripheral and Central Mechanisms / 神经科学通报·英文版

Increasing evidence suggests that cytokines and chemokines play crucial roles in chronic itch. In the present study, we evaluated the roles of tumor necrosis factor-alpha (TNF-α) and its receptors TNF receptor subtype-1 (TNFR1) and TNFR2 in acute and chronic itch in mice. Compared to wild-type (WT) mice, TNFR1-knockout (TNFR1-KO) and TNFR1/R2 double-KO (DKO), but not TNFR2-KO mice, exhibited reduced acute itch induced by compound 48/80 and chloroquine (CQ). Application of the TNF-synthesis inhibitor thalidomide and the TNF-α antagonist etanercept dose-dependently suppressed acute itch. Intradermal injection of TNF-α was not sufficient to evoke scratching, but potentiated itch induced by compound 48/80, but not CQ. In addition, compound 48/80 induced TNF-α mRNA expression in the skin, while CQ induced its expression in the dorsal root ganglia (DRG) and spinal cord. Furthermore, chronic itch induced by dry skin was reduced by administration of thalidomide and etanercept and in TNFR1/R2 DKO mice. Dry skin induced TNF-α expression in the skin, DRG, and spinal cord and TNFR1 expression only in the spinal cord. Thus, our findings suggest that TNF-α/TNFR1 signaling is required for the full expression of acute and chronic itch via peripheral and central mechanisms, and targeting TNFR1 may be beneficial for chronic itch treatment.

Spinal Mechanisms of Itch Transmission / 神经科学通报·英文版

Peripheral itch stimuli are transmitted by sensory neurons to the spinal cord dorsal horn, which then transmits the information to the brain. The molecular and cellular mechanisms within the dorsal horn for itch transmission have only been investigated and identified during the past ten years. This review covers the progress that has been made in identifying the peptide families in sensory neurons and the receptor families in dorsal horn neurons as putative itch transmitters, with a focus on gastrin-releasing peptide (GRP)-GRP receptor signaling. Also discussed are the signaling mechanisms, including opioids, by which various types of itch are transmitted and modulated, as well as the many conflicting results arising from recent studies.

Modulation of Pain and Itch by Spinal Glia / 神经科学通报·英文版

Chronic pain and itch are a pathological operation of the somatosensory system at the levels of primary sensory neurons, spinal cord and brain. Pain and itch are clearly distinct sensations, and recent studies have revealed the separate neuronal pathways that are involved in each sensation. However, the mechanisms by which these sensations turn into a pathological chronic state are poorly understood. A proposed mechanism underlying chronic pain and itch involves abnormal excitability in dorsal horn neurons in the spinal cord. Furthermore, an increasing body of evidence from models of chronic pain and itch has indicated that synaptic hyperexcitability in the spinal dorsal horn might not be a consequence simply of changes in neurons, but rather of multiple alterations in glial cells. Thus, understanding the key roles of glial cells may provide us with exciting insights into the mechanisms of chronicity of pain and itch, and lead to new targets for treating chronic pain and itch.

Chemokine Receptor CXCR3 in the Spinal Cord Contributes to Chronic Itch in Mice / 神经科学通报·英文版

Recent 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 that Cxcr3 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 reduced in Cxcr3 mice. In addition, the expression of CXCR3 and CXCL10 was increased in the spinal cord in the dry skin model induced by acetone and diethyl ether followed by water (AEW). Intrathecal injection of a CXCR3 antagonist alleviated AEW-induced itch. Furthermore, touch-elicited itch (alloknesis) after compound 48/80 or AEW treatment was suppressed in Cxcr3 mice. Finally, AEW-induced astrocyte activation was inhibited in Cxcr3 mice. Taken together, these data suggest that spinal CXCR3 mediates chronic itch and alloknesis, and targeting CXCR3 may provide effective treatment for chronic pruritus.

Spinal Circuits Transmitting Mechanical Pain and Itch / 神经科学通报·英文版

In 1905, Henry Head first suggested that transmission of pain-related protopathic information can be negatively modulated by inputs from afferents sensing innocuous touch and temperature. In 1965, Melzak and Wall proposed a more concrete gate control theory of pain that highlights the interaction between unmyelinated C fibers and myelinated A fibers in pain transmission. Here we review the current understanding of the spinal microcircuits transmitting and gating mechanical pain or itch. We also discuss how disruption of the gate control could cause pain or itch evoked by innocuous mechanical stimuli, a hallmark symptom for many chronic pain or itch patients.