Itch Sensation Research Articles

Novel inhibitory brainstem neurons with selective projections to spinal lamina I reduce both pain and itch.

Sensory information is transmitted from peripheral nerves, through the spinal cord, and up to the brain (“bottom up” pathway). Some of this information may be modulated by “top‐down” projections from the brain to the spinal cord. Discovering endogenous mechanisms for reducing pain and itch holds enormous potential for developing new treatments. However, neurons mediating the top‐down inhibition of pain are not well understood, nor has any such pathway been identified for itch sensation. Here, we identify a novel population of GABAergic neurons in the ventral brainstem, distinguished by prodynorphin expression, which we named LJA5. LJA5 neurons provide the only known inhibitory projection specifically to lamina I of the spinal cord, which contains sensory neurons that transmit pain and itch information up to the brain. Chemogenetically activating LJA5 neurons in male mice reduces capsaicin‐induced pain and histamine‐induced itch. Identifying this new pathway opens new treatment opportunities for chronic, refractory pain, and pruritis.

15620 Paederus dermatitis involving the periocular area: An observational study from Nepal

Background: Paederus dermatitis involving the periocular area, also known as Nairobi ey,e is characterized by erythematous vesiculobullous linear patch or plaque with itching, stinging, or burning sensation. It commonly occurs during rainy season and near to the agricultural fields.

Direct evidence that the brain reward system is involved in the control of scratching behaviors induced by acute and chronic itch

In the present study, we demonstrated that there is a direct relationship between scratching behaviors induced by itch and functional changes in the brain reward system. Using a conditional place preference test, the rewarding effect was clearly evoked by scratching under both acute and chronic itch stimuli. The induction of ΔFosB, a member of the Fos family of transcription factors, was observed in dopamine transporter (DAT)-positive dopamine neurons in the ventral tegmental area (VTA) of mice suffering from a chronic itch sensation. Based on a cellular analysis of scratching-activated neurons, these neurons highly expressed tyrosine hydroxylase (TH) and DAT genes in the VTA. Furthermore, in an in vivo microdialysis study, the levels of extracellular dopamine in the nucleus accumbens (NAcc) were significantly increased by transient scratching behaviors. To specifically suppress the mesolimbic dopaminergic pathway using pharmacogenetics, we used the TH-cre/hM4Di mice. Pharmacogenetic suppression of mesolimbic dopaminergic neurons significantly decreased scratching behaviors. Under the itch condition with scratching behaviors restricted by an Elizabethan collar, the induction of ΔFosB was found mostly in corticotropin-releasing hormone (CRH)-containing neurons of the hypothalamic paraventricular nucleus (PVN). These findings suggest that repetitive abnormal scratching behaviors under acute and chronic itch stimuli may activate mesolimbic dopamine neurons along with pleasant emotions, while the restriction of such scratching behaviors may initially induce the activation of PVN-CRH neurons associated with stress.

MRGPRX2 sensing of cationic compounds-A bridge between nociception and skin diseases?

Mast cells are innate immune cells located at many barrier sites in the body and known to protect the host against environmental threats and to be involved in allergic diseases. More recently, new studies have investigated their roles in the regulation of skin inflammation and transmission of pain and itch sensations. Mast cell signalling through the Mas-related G protein-coupled receptor (MRGPR) X2 or its mouse orthologue MRGPRB2 has been reported to be one of the major mechanism by which mast cell can regulate such processes. MRGPRX2 and MRGPRB2 can induce mast cell degranulation upon binding to a broad panel of cationic molecules such as neuropeptides, bacteria-derived quorum sensing molecules, venom peptides, host defense peptides and, unfortunately, various FDA-approved drugs. Upon activation, mast cells release granule-associated proteases, lipids and multiple cytokines that can modulate vascular permeability, immune cells recruitment and activation status of tissue-projecting nociceptive sensory neurons (ie nociceptors). Here, we discuss the modality of MRGPRX2-dependent mast cell activation and its different consequences on the patterns of skin inflammation and associated diseases. We notably emphasize how MRGPRX2-dependent skin mast cell activation might trigger various pathological traits such as pruritus, pain and inflammation and therefore become a potential therapeutic target for inflammatory pain, itch, atopic dermatitis and drugs-induced injection site reactions.

FGF13 Is Required for Histamine-Induced Itch Sensation by Interaction with NaV1.7.

Itch can be induced by activation of small-diameter DRG neurons, which express abundant intracellular fibroblast growth factor 13 (FGF13). Although FGF13 is revealed to be essential for heat nociception, its role in mediating itch remains to be investigated. Here, we reported that loss of FGF13 in mouse DRG neurons impaired the histamine-induced scratching behavior. Calcium imaging showed that the percentage of histamine-responsive DRG neurons was largely decreased in FGF13-deficient mice; and consistently, electrophysiological recording exhibited that histamine failed to evoke action potential firing in most DRG neurons from these mice. Given that the reduced histamine-evoked neuronal response was caused by knockdown of FGF13 but not by FGF13A deficiency, FGF13B was supposed to mediate this process. Furthermore, overexpression of histamine Type 1 receptor H1R, but not H2R, H3R, nor H4R, increased the percentage of histamine-responsive DRG neurons, and the scratching behavior in FGF13-deficient mice was highly reduced by selective activation of H1R, suggesting that H1R is mainly required for FGF13-mediated neuronal response and scratching behavior induced by histamine. However, overexpression of H1R failed to rescue the histamine-evoked neuronal response in FGF13-deficient mice. Histamine enhanced the FGF13 interaction with NaV1.7. Disruption of this interaction by a membrane-permeable competitive peptide, GST-Flag-NaV1.7CT-TAT, reduced the percentage of histamine-responsive DRG neurons, and impaired the histamine-induced scratching, indicating that the FGF13/NaV1.7 interaction is a key molecular determinant in the histamine-induced itch sensation. Therefore, our study reveals a novel role of FGF13 in mediating itch sensation via the interaction of NaV1.7 in the peripheral nervous system.SIGNIFICANCE STATEMENT Scratching induced by itch brings serious tissue damage in chronic itchy diseases, and targeting itch-sensing molecules is crucial for its therapeutic intervention. Here, we reveal that FGF13 is required for the neuronal excitation and scratching behavior induced by histamine. We further provide the evidence that the histamine-evoked neuronal response is mainly mediated by histamine Type 1 receptor H1R, and is largely attenuated in FGF13-deficent mice. Importantly, we identify that histamine enhances the FGF13/NaV1.7 interaction, and disruption of this interaction reduces histamine-evoked neuronal excitation and highly impairs histamine-induced scratching behavior. Additionally, we also find that FGF13 is involved in 5-hydroxytryptamine-induced scratching behavior and hapten 1-fluoro-2,4-dinitrobenzene-induced chronic itch.

Clinical analysis of 126 patients with coronavirus disease 2019 with pharyngeal symptoms

Objective: To investigate the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with pharyngeal symptoms. Methods: From January 10 to May 15, 2020, clinical data of 1 228 patients with COVID-19 in Renmin Hospital of Wuhan University was collected (554 males and 674 females, with the range of age from 10 to 95 years old, the average age was 55.2 years old). The patients were divided into pharyngeal symptoms group (PS, 126 cases) and non-pharyngeal symptoms group (Non-PS, 1 102 cases) according to the presence or absence of pharyngeal symptoms such as pharyngalgia, pharyngeal dryness, pharyngeal itching, and pharyngeal foreign body sensation. The clinical data in terms of age, sex, medical history, duration of symptoms, treatment time, clinical classification, pulmonary imaging findings, whole blood cell count, serum hypersensitivity C-reactive protein, C-reactive protein, procalcitonin were statistically analyzed between the two groups. Chi-square, Fisher's exact test and Mann-Whitney U test were used for statistical analysis. Results: The most common pharyngeal symptoms were pharyngalgia (59.52%, 75/126), followed by foreign body sensation (23.02%, 29/126), pharyngeal dryness (8.73%, 11/126), and itching (8.73%, 11/126). The median age of the patients in the PS group was 51.50 years old, which was less than 57.50 years old in the non-PS group, showing a significant difference (P<0.05). The female cases accounted for 65.08% (82/126), which was higher than 53.72% (592/1 102) of the non-PS group (P<0.05). The incidence of bilateral lung inflammation confirmed by CT images was 73.81% (93/126), which was significantly lower than 83.48% (920/1 102) in the non-PS group (P<0.05). No significant differences were shown in the proportion of patients with clinical types, treatment days, duration of symptoms, white blood cell count, lymphocyte count, lymphocyte percentage, eosinophil count, eosinophil percentage, hypersensitive C-reactive protein, C-reactive protein, D-dimer, procalcitonin and other indicators (P>0.05). Conclusions: The incidence of pharyngeal symptoms in patients with COVID-19 is 10.26%. Most of these symptoms occur before or at the same time as the common symptoms of the disease. Therefore, patients with such symptoms may bring a greater risk of infection to otolaryngologist. According to the current clinical classification criteria, pharyngeal symptoms have no obvious correlation with the degree of the disease; but the presence of pharyngeal symptoms may suggest a milder clinical presentation and a better prognosis.

The TRPM3 ion channel mediates nociception but not itch evoked by endogenous pruritogenic mediators

During the molecular transduction of itch, the stimulation of pruriceptors on sensory fibers leads to the activation or sensitization of ion channels, which results in a consequent depolarization of the neurons. These ion channels mostly belong to the transient receptor potential (TRP) channels, which are involved in nociception and thermosensation. In particular, TRPV1 and TRPA1 were described in the transduction of both thermal nociception as well as histaminergic and non-histaminergic itch. The thermosensitive TRPM3 plays an indispensable role in heat nociception together with TRPV1 and TRPA1. However, the role of TRPM3 in the development of pruritus has not been studied yet. Therefore, in this study we aimed at investigating the potential role of TRPM3 in the transduction of pruritus and pain by investigating itch- and nociception-related behavior of Trpm3+/+ and Trpm3−/− mice, and by studying the activation of somatosensory neurons isolated from trigeminal ganglia upon application of algogenic and pruritogenic substances. Activators of TRPM3 evoked only nocifensive responses, but not itch in Trpm3+/+ animals, and these nocifensive responses were abolished in the Trpm3−/− strain. Histamine and endogenous non-histaminergic pruritogens induced itch in both Trpm3+/+ and Trpm3−/− mice to a similar extent. Genetic deletion or pharmacological blockade diminished TRPM3 mediated Ca2+ responses of sensory neurons, but did not affect responses evoked by pruritogenic substances. Our results demonstrate that, in contrast to other thermosensitive TRP channels, TRPM3 selectively mediates nociception, but not itch sensation, and suggest that TRPM3 is a promising candidate to selectively target pain sensation.

The features of complex therapy of bacterial vaginosis in pregnant women with cervical incompetence

Objective of the study: to study the clinical and laboratory efficacy of the Femivag® (contains Lactobacillus gasseri, Lactobacillus rhamnosus) drug in the complex treatment of bacterial vaginosis (BV) in pregnant women with high risk of preterm birth.Materials and methods. 42 pregnant women at the 16–18 weeks of gestation with cervical dysfunction and BV diagnosed before cervical pessary installation were examined and treated. All patients were assessed the dynamics of symptoms severity, performed PCR testі with a quantitative count of opportunistic pathogens and Lactobacillus spp. Perinatal and neonatal outcomes were also assessed. Femivag® vaginal capsules were prescribed to 24 women (main group) to restore the vaginal microbiota after BV treatment. 18 pregnant women used dietary supplements containing pro- and prebiotics (comparison group). The examination was performed before treatment, 4 and 15–16 days from the therapy start, 4 and 8 weeks after treatment.Results. Vaginal probiotic Femivag® as a component of complex therapy of BV before the installation of cerclage pessary was more effective than the oral food supplements with pro- and prebiotics in terms of reducing in vaginal discharge and vaginal discomfort, the disappearance of vaginal itching and burning sensation for 4 days of therapy. Gardnerella vaginalis / Prevotella bivia / Porphyromonas spp., Mobiluncus spp. / Corynebacterium spp. and Atopobium vaginae disappeared and vaginal normobiota significant recovered in the second trimester in women with cervical dysfunction at 4 and 8 weeks from the start of BV treatment with Femivag®. Frequency of premature rupture of membranes and chorioamnionitis significantly decreased in the main group. Femivag® was well tolerated and had no side effects.Conclusions. Femivag® vaginal capsules had a pronounced clinical and laboratory effect in the complex treatment of BV in pregnant women with incompetent cervix

A spinal neural circuitry for converting touch to itch sensation

Touch and itch sensations are crucial for evoking defensive and emotional responses, and light tactile touch may induce unpleasant itch sensations (mechanical itch or alloknesis). The neural substrate for touch-to-itch conversion in the spinal cord remains elusive. We report that spinal interneurons expressing Tachykinin 2-Cre (Tac2Cre) receive direct Aβ low threshold mechanoreceptor (LTMR) input and form monosynaptic connections with GRPR neurons. Ablation or inhibition markedly reduces mechanical but not acute chemical itch nor noxious touch information. Chemogenetic inhibition of Tac2Cre neurons also displays pronounced deficit in chronic dry skin itch, a type of chemical itch in mice. Consistently, ablation of gastrin-releasing peptide receptor (GRPR) neurons, which are essential for transmitting chemical itch, also abolishes mechanical itch. Together, these results suggest that innocuous touch and chemical itch information converge on GRPR neurons and thus map an exquisite spinal circuitry hard-wired for converting innocuous touch to irritating itch.

Evidence of Pepsin-Related Ocular Surface Damage and Dry Eye (PROD Syndrome) in Patients with Laryngopharyngeal Reflux

Background: patients with laryngopharyngeal reflux (LPR) showed detectable levels of tear pepsin that explain the nasolacrimal obstruction. The purpose of this study was to determine whether patients with LPR show ocular surface changes and to investigate the relationship between lacrimal pepsin concentration and ocular alterations. Methods: Fifty patients with positive endoscopic signs for LPR and an equal or higher score of 13 and 7 for Reflux Symptom Index and Reflux Finding Score were enrolled. Twenty healthy patients with no reflux disease and dry eye were included as the control group. After evaluation of ocular discomfort symptoms, the tear break-up time test, corneal staining, and tear sampling were performed. Tear pepsin levels were measured using Pep-testTM kit. Results: Patients with LPR showed ocular surface changes including epithelial damage (48%) and impairment of lacrimal function (72%). Tear pepsin levels were detectable in 32 out of 50 (64%) patients with LPR (mean ± SD: 55.4 ± 67.5 ng/mL) and in none of the control subjects. Most of the LPR patients complained of ocular discomfort symptoms, including itching (38%), redness (56%), or foreign body sensation (40%). Tear pepsin levels were significantly correlated with the severity of LPR disease and with ocular surface changes. Conclusions: A multidisciplinary approach, including ophthalmological evaluation, should be considered in order to improve the management of patients with LPR.

Mechanisms of broad-band ultraviolet B irradiation-induced itch in mice

Abstract Although sunburn can produce severe uncontrollable itching, the underlying mechanisms of ultraviolet (UV) irradiation-induced itch are poorly understood because of a lack of experimental animal models of sunburn itch. Here we established a sunburn-related mouse model and found that Broad-band UVB (BB-UVB) irradiation elicited scratching but not wiping behavior in mice. By using a combination of live-cell Ca2+ imaging and quantitative RT-PCR on dorsal root ganglion (DRG) neurons, hematoxylin and eosin staining, immunofluorescence staining of skin preparations, behavioral testing, in combination with genetic and pharmacological approaches, we showed that TRPV1-positive DRG neurons but not mast cells are involved in BB-UVB irradiation-induced itch. Moreover, both genetic and pharmacological inhibition of TRPV1 function significantly alleviated BB-UVB irradiation-induced itch response. Collectively, our results suggest that BB-UVB irradiation evokes itch sensation in mice through promoting TRPV1 channel function in DRG neurons and provide potential therapeutic targets for sunburn-related itch.

Bacterial agents and changes in drug susceptibilities in cases of chronic dacryocystitis, Southern China

This study aimed to determine the susceptibility and the changes of bacterial agents of chronic dacryocystitis and determine the risk factors for bacterial prevalence and drug sensitivity to provide a reference for clinical selection of antibiotics. A case-control study was conducted using 112 patients with chronic dacryocystitis and 112 patients with non-infectious ophthalmopathy between August 2017 and April 2018. Lacrimal and conjunctival sac secretions were cultured for aerobic and anaerobic bacteria. Forty-five patients with chronic dacryocystitis between November 2014 and November 2015 were also included. Positive bacterial cultures were obtained from 61.9% and 50.9% of chronic dacryocystitis and non-infectious ophthalmopathy patients, but the detection rates for pathogenic bacteria were 18.3% and 2.7%, respectively (P > 0.001). Gram-negative and anaerobic bacteria were significantly more prevalent in the patient group compared with the control group (P = 0.001 and 0.005, respectively). Bacteria were detected at a significantly higher rate in patients with irritant symptoms (itch or foreign-body sensation) than in those without (OR = 9.333, P = 0.002), particularly Staphylococcus (OR = 9.783, P = 0.002). 11.6% (10/86) and 55.8% (48/86) showed resistance to levofloxacin and tobramycin, respectively. Compared with three years ago, the detection rate for Gram-positive cocci decreased from 51.1% to 27.8% (χ2 = 8.054, P = 0.005) CONCLUSIONS: Gram-positive cocci, Gram-negative bacilli, and anaerobic bacteria were the predominant pathogens. The prevalence of Gram-positive bacteria in cases of chronic dacryocystitis is decreasing.

STUDY TO ANALYZE THE DRUG SENSITIVITY PROFILE OF THE PATIENTS SUFFERING FROM SORE THROAT: AN OBSERVATIONAL STUDY.

Aim: to analyze the drug sensitivity profile of the patients suffering from sore throat.&#x0D; Materials and Methods: The present prospective observational study was conducted in the Department of ENT, Sri Krishna Medical College and Hospital, Muzaffarpur, Bihar. Among 200 patients of either gender and of any age group attended the OPD of the ENT presented with the complaint of sore throat, throat pain, throat irritation, throat itching and foreign body sensation were recruited. A thorough ENT examination is done including ear examination, throat examination, and nasal examination. Throat swab samples collected through a sterile culture sensitivity tube and sent to microbiological lab and culture sensitivity reports collected from the patients during follow up visits.&#x0D; Results: majority of the patients were male 58.5% and rest 41.5% were female. Gram negative organisms are detected in (70.5%), Gram positive organisms detected (21.0%), and no organism detected (8.5%) of the swab samples.&#x0D; Conclusion: gram positive organisms were resistant to benzyl penicillin or ampicillin, clindamycin, ciprofloxacin or levofloxacin and sensitive to tetracycline, gentamicin, linezolid. Gram negative organisms were resistant to ampicillin, amoxyclav and sensitive to pipracillin or tazobactum, cefoperazone, amikacin, gentamicin, imipenem, cefepime, ciprofloxacin.&#x0D; Keywords: couture, throat swab, gram positive, gram negative, throat infection

Advances in Understanding the Initial Steps of Pruritoceptive Itch: How the Itch Hits the Switch.

Pruritoceptive (dermal) itch was long considered an accompanying symptom of diseases, a side effect of drug applications, or a temporary sensation induced by invading pruritogens, as produced by the stinging nettle. Due to extensive research in recent years, it was possible to provide detailed insights into the mechanism of itch mediation and modulation. Hence, it became apparent that pruritus is a complex symptom or disease in itself, which requires particular attention to improve patients’ health. Here, we summarize recent findings in pruritoceptive itch, including how this sensation is triggered and modulated by diverse endogenous and exogenous pruritogens and their receptors. A differentiation between mediating pruritogen and modulating pruritogen seems to be of great advantage to understand and decipher the molecular mechanism of itch perception. Only a comprehensive view on itch sensation will provide a solid basis for targeting this long-neglected adverse sensation accompanying numerous diseases and many drug side effects. Finally, we identify critical aspects of itch perception that require future investigation.

The effect of Quercus (Oak Gal) vaginal cream versus metronidazole vaginal gel on bacterial vaginosis: A double‑blind randomized controlled trial

Objective: This study was aimed to compare the effect of an Oak Gall extract‑based cream and a metronidazole Gel on the bacterial vaginosis among women in reproductive age. Material and methodsThis was a double-blind, randomized controlled trial performed on 84 women with BV in reproductive age. Accordingly, the women were randomly assigned to the Oak Gall (n = 42) or metronidazole (n = 42) groups. Diagnosis of BV was confirmed when at least 3 of the 4 Amsel criteria were met by the participants (whitish-grey or thin homogeneous discharge, pH ≥ 4.5, the release of a fishy odor on the addition of 10 % KOH, and detection of clue cells > 20 % in the microscopic examination). For each group, either a methanol extract of Oak Gall vaginal cream or a metronidazole vaginal gel (5 g) was used as intravaginal for 5 consecutive days, and all the signs or symptoms were assessed by passing 4–7 days from the treatment completion. ResultsAt baseline, the two groups were homogenous in terms of the vaginal burning, odor, dysuria, dyspareunia, and itching. Also, all women in both groups were free of symptoms (vaginal itching and burning sensation, bad odor, dysuria, and dyspareunia) by passing one week from the intervention (p < 0.001). The percent of bacterial vaginosis treatment was in 33(82.1 %) patients in terms of Oak Gall group and in 34(87.5 %) patients of Metronidazole group (p=0.56).Notably, Oak Gall was as effective and safe as metronidazole in the treatment of BV in reproductive-aged women. ConclusionOak Gall could be recommended for women in reproductive age who are uncomfortable with the potential side effects of synthetic drugs.

Topical Application of ASN008, a Permanently Charged Sodium Channel Blocker, Shows Robust Efficacy, a Rapid Onset, and Long Duration of Action in a Mouse Model of Pruritus.

The sensation of pruritus, or itch, is associated with a variety of skin and medical disorders. Itch is transmitted through afferent C-fibers, and sodium channels play a key role in the transmission process. Local anesthetics, which block sodium channels, are used topically to treat itch but generally have a short duration of action and are not selective for afferent nerves underlying the itch sensation. Accordingly, there is a substantial unmet need for safe, efficacious, long-acting treatments for chronic pruritus, including nonhistaminergic itch. We investigated the dose-response, time to onset, and duration of action of ASN008 topical gel, which targets small afferent sodium channels, in a murine model of pruritus in which scratching behavior is induced by intradermal injection of chloroquine into the nape of the neck of C57BL/6 mice. Topical application of ASN008 gel resulted in a concentration-dependent reduction of scratching behavior. Onset of action was ≤1 hour, and duration of scratching inhibition was 15-24 hours. In a further study involving once-daily application for 5 days with chloroquine challenge on day 5, treatment with ASN008 gel again resulted in a concentration-dependent reduction of chloroquine-induced scratching, even when the gel was removed 3 hours after each daily application. In conclusion, topical ASN008 gel produces a dose-dependent reduction of scratching in a mouse model of pruritus, with a rapid onset and long duration of action, and may prove to be an effective, once-daily treatment of a variety of pruritic conditions in humans, including nonhistaminergic itch. SIGNIFICANCE STATEMENT: ASN008 gel produces a dose-dependent reduction of scratching in a mouse model of pruritus, with a rapid onset and long duration of action, and may prove to be an effective, once- or twice-daily treatment for a variety of pruritic conditions in humans. ASN008 gel has demonstrated good safety and tolerability in healthy volunteers and is currently under investigation in a phase 1b clinical study to evaluate safety, tolerability, pharmacokinetics, and preliminary antipruritic efficacy in atopic dermatitis patients (ClinicalTrials.gov ID: NCT03798561).

Neuropathic pruritus associated with brain disorders

Various types of brain pathology may be associated with neuropathic pruritus. While the mechanisms behind neuropathic itch is not well understood, damage to the itch processing centers and circuits of the brain may lead to changes in signaling in both top-down and bottom-up pathways that results in the distortion of itch sensation. Patients with brain pathologies such as such as stroke, brain tumors, spongiform encephalopathies, multiple sclerosis, trigeminal trophic syndrome, and systemic diseases such as end-stage renal diseases and primary biliary cholangitis have reported neuropathic itch of different characteristics. Commonly involved areas of the brain that, when damaged, are associated with neuropathic itch are the primary somatosensory cortex, precuneus, hippocampus, amygdala, periaqueductal gray, thalamus, insula, nucleus accumbens, Gasserian ganglion, cerebellum, cingulate cortex, prefrontal cortex, medulla, frontotemporal, and parietal lobe. Treatments for neuropathic pain, depression and seizures, such as kappa opioids, gabapentinoids, tricyclic antidepressants, and ketamine, are commonly used to treat neuropathic pruritus and are found to be effective.

Inhibition of M/Kv7 Currents Contributes to Chloroquine-Induced Itch in Mice.

M/Kv7 potassium channels play a key role in regulation of neuronal excitability. Modulation of neuronal excitability of primary sensory neurons determines the itch sensation induced by a variety of itch-causing substances including chloroquine (CQ). In the present study, we demonstrate that suppression of M/Kv7 channel activity contributes to generation of itch in mice. CQ enhances excitability of the primary sensory neurons through inhibiting M/Kv7 potassium currents in a Ca2+ influx-dependent manner. Specific M/Kv7 channel opener retigabine (RTG) or tannic acid (TA) not only reverses the CQ-induced enhancement of neuronal excitability but also suppresses the CQ-induced itch behavior. Systemic application of RTG or TA also significantly inhibits the itch behavior induced by a variety of pruritogens. Taken together, our findings provide novel insight into the molecular basis of CQ-induced itch sensation in mammals that can be applied to the development of strategies to mitigate itch behavior.

772 Terminal arborizations of itch-sensing neurons exhibit large receptive field in the skin and regionally specific organization in the spinal cord

Itch sensation is initiated by the activation of a specific subset of sensory neurons that project their peripheral and central axons to the skin and spinal cord respectively. Different subtypes of sensory neurons exhibit distinct terminal arborization subserving their functions. Sensory arborization of itch-sensing neurons has never been observed due to the lack of proper molecular genetic tool. Here we have genetically labeled a small subset of DRG sensory neurons using a newly generated MrgprC11CreER mouse line.

Functional and anatomical brain connectivity in psoriasis patients and healthy controls: a pilot brain imaging study after exposure to mentally induced itch.

Despite the prevalence of psoriasis, the processing of itch in psoriasis and its impact on the central nervous system (CNS) remain unclear. We studied the influence of psoriasis on the CNS using magnetic resonance imaging techniques (fMRI and DTI, respectively) to investigate whether mentally induced itch can modify the functional connectivity or the white matter microstructure of the brain. Fourteen patients with chronic psoriasis and 15 healthy controls were recruited. Itch was mentally induced in subjects by videos showing others scratching themselves. The observation of functional connectivity during the viewing the video revealed an interconnected network of brain regions that are more strongly coupled in psoriasis patients than in healthy controls. This network links the cerebellum, the thalami, the anteroposterior cingulum, the inferior parietal lobules, the middle temporal poles and the parahippocampal, hippocampal, lingual and supramarginal gyri. We also found connections with the right precuneus and both left insula and superior temporal gyrus. The DTI analysis showed that chronic itch affects the microstructure of white matter, including the anterior thalamic radiations, the superior and inferior longitudinal fasciculi, the corticospinal tracts, the cingulum, the external capsules, the inferior frontal-occipital fasciculi and both minor and major forceps. Our results indicate that there could exist a network which is more interconnected in psoriasis patients. Among two building blocks of this network, the subnetwork encoding the perception and control of itch sensation is more affected than the subnetwork representing mentalizing and empathy. With an approach consisting of measuring microstructural changes at a local level in the brain, we also contradict the findings obtained with global measures which stated that chronic psoriasis cannot alter the anatomy of the brain. This confirms that itchy pathophysiological conditions have similar effects on functional and structural connectivity as those observed in chronic pain.