Itch Sensation Research Articles

Activation of serotonin receptor 2 by glucosylsphingosine can be enhanced by TRPA1 but not TRPV1: Implication of a novel glucosylsphingosine-mediated itch pathway

Glucosylsphingosine (GS) is an endogenous sphingolipid that specifically accumulates in the skin of patients with atopic dermatitis (AD). Notably, it was recently found that GS can induce itch sensation by activating serotonin receptor 2A and TRPV4 ion channels. However, it is still uncertain whether other molecules are involved in GS-induced itch sensation. Therefore, by using the calcium imaging technique, we investigated whether serotonin receptor 2 – specifically 2A and 2B – can interact with TRPV1 and TRPA1, because these are representative ion channels in the transmission of itch. As a result, it was found that GS did not activate TRPV1 or TRPA1 per se. Moreover, cells expressing both serotonin receptor 2 and TRPV1 did not show any changes in calcium responses. However, enhanced calcium responses were observed in cells expressing serotonin receptor 2 and TRPA1, suggesting a possible interaction between these two molecules. Similar synergistic effects were also observed in cells expressing serotonin receptor 2 and TRPA1, but not TRPV1. Furthermore, a phospholipase C inhibitor (U73122) and a store-operated calcium entry blocker (SKF96365) significantly reduced GS-induced responses in cells expressing both serotonin receptor 2 and TRPA1, but not with pre-treatment with a Gβγ-complex blocker (gallein). Therefore, we propose a putative novel pathway for GS-induced itch sensation, such that serotonin receptor 2 could be coupled to TRPA1 but not TRPV1 in sensory neurons.

405 Atopic dermatitis patients have decreased epidermal innervation but increased neuronal substance p expression

Severe pruritus in atopic dermatitis (AD) significantly impairs patients’ quality of life, primarily due to relentless itching. Sensory nerves in the epidermis are important in mediating sensation of itch, but there is conflicting evidence whether epidermal nerve density is increased or decreased in lesional skin of AD. Here we measured nerve length, branching, and neurotransmitter expression in epidermis of healthy controls and lesional and non-lesional skin of AD patients. Four millimeter punch biopsies were taken from skin of 8 healthy adult control patients and 8 lesional and non-lesional skin of patients with moderate-to-severe AD.

Miswiring of Merkel cell and pruriceptive C fiber drives the itch-scratch cycle.

Itch sensation provokes the scratch reflex to protect us from harmful stimuli in the skin. Although scratching transiently relieves acute itch through activation of mechanoreceptors, it propagates the vicious itch-scratch cycle in chronic itch by further aggravating itch over time. Although well recognized clinically, the peripheral mechanisms underlying the itch-scratch cycle remain poorly understood. Here, we show that mechanical stimulation of the skin results in activation of the Piezo2 channels on Merkel cells that pathologically promotes spontaneous itch in experimental dry skin. Three-dimensional reconstruction and immunoelectron microscopy revealed structural alteration of MRGPRA3+ pruriceptor nerve endings directed toward Merkel cells in the setting of dry skin. Our results uncover a functional miswiring mechanism under pathologic conditions, resulting in touch receptors triggering the firing of pruriceptors in the skin to drive the itch-scratch cycle.

Ayurvedic management of Ekakushtha (Chronic Plaque Psoriasis) – A Case Report

Psoriasis is one of the common skin diseases encountered in world population which is characterized by sharply demarcated erythematous papules and plaques. Prevalence of psoriasis is 0.1 to 3 per cent worldwide. Psoriasis occurs equally in both genders, most commonly in second to fourth decade of life. In this paper, a case report of patient with (Ekakushtha) Chronic Plaque Psoriasis is discussed with successful Ayurvedic treatment. A 25-year-old female patient came with complaints of reddish lesions over arms, forearms, legs, thighs and trunk region; itching and burning sensation over lesion and scalp; scaling over scalp region since five years. The condition was diagnosed as Ekakushtha according to Ayurved and the treatment was planned accordingly. The patient was treated with Ayurvedic oral medications, local applications and Pathya (wholesome diet) regimen without any Panchakarma therapy. Ayurvedic management has given her better results within 45 days from commencement of treatment.

PIEZO1 transduces mechanical itch in mice

Itch triggers scratching, a behavioural defence mechanism that aids in the removal of harmful irritants and parasites1. Chemical itch is triggered by many endogenous and exogenous cues, such as pro-inflammatory histamine, which is released during an allergic reaction1. Mechanical itch can be triggered by light sensations such as wool fibres or a crawling insect2. In contrast to chemical itch pathways, which have been extensively studied, the mechanisms that underlie the transduction of mechanical itch are largely unknown. Here we show that the mechanically activated ion channel PIEZO1 (ref. 3) is selectively expressed by itch-specific sensory neurons and is required for their mechanically activated currents. Loss of PIEZO1 function in peripheral neurons greatly reduces mechanically evoked scratching behaviours and both acute and chronic itch-evoked sensitization. Finally, mice expressing a gain-of-function Piezo1 allele4 exhibit enhanced mechanical itch behaviours. Our studies reveal the polymodal nature of itch sensory neurons and identify a role for PIEZO1 in the sensation of itch.

Neuromodulatory Effects of Adjunctive High Definition Transcranial Direct Current Stimulation (HDtDCS) on Auditory Verbal Hallucinations in Schizophrenia Patients: A Sham Controlled Diffusion Tensor Imaging Study

AimsTo see the neuromodulatory effects of adjunctive HD-tDCS on white matter connectivity by using Diffusion Tensor Imaging (DTI) in schizophrenia patients with Auditory Verbal Hallucinations (AVH)MethodsThis was a randomized, double blind, sham controlled study. 40 patients of schizophrenia with prominent auditory verbal hallucinations and 10 age sex matched healthy controls were selected. The patients were randomly assigned to 2 groups and were given active or sham adjunctive HDtDCS (Active Treatment = 10 sessions of 2 mA current applied for 20 minutes, twice daily for 5 days, at left temporo-parietal Junction (TPJ); Sham treatment = 10 sessions of 1 mA current, twice daily for 5 days was applied for 30 sec at left TPJ). Fractional anisotropy of left arcuate fasciculus by Diffusion tensor imaging was assessed and severity of schizophrenia symptoms and auditory hallucinations were rated on PANSS and PSYRATS-AH at baseline, after 1st week (i.e. end of HDtDCS sessions) and 4 weeks after the end of the HDtDCS sessions). Patients received stable dose of antipsychotics for the total study duration (equivalent to or more than 400 mg of chlorpromazine) to eliminate confounding bias. Fractional anisotropy of left arcuate fasciculus by Diffusion tensor imaging was assessed in healthy controls. DTI data were analysed by DSI Studio software. Statistical analysis was done by SPSS version 25.Results1.Both the patient groups were comparable with regard to socio-demographic variables and baseline clinical variables.2.There was no significant difference in the values of Fractional Anisotropy in Left Arcuate Fasciculus among the patients and healthy controls at baseline.3.The group receiving active adjunctive HDtDCS, showed significant improvement in the frequency domain of AVH over time, in time*group comparison by repeat measure ANOVA with Mauchly's test of sphericity and Greenhouse-Geisser correction [p = 0.011 and partial eta square = 0.129].4.There was no significant difference in change in the Fractional anisotropy of the left arcuate fasciculus noted between the groups over time.5.Application of HDtDCS was not associated with significant side effects, minor itching and mild burning sensation being the only reported side effectsConclusionAdjunctive active HD-tDCS to the left temporo-parietal junction showed a statistically significant improvement in frequency of auditory verbal hallucinations (AVH) in schizophrenia patients, when compared to sham stimulation.

Individual Differences in Conversational Self-Touch Frequency Correlate with State Anxiety

Self-touches are frequently performed in everyday conversations. Although self-touch appears to relate to itching skin sensations or grooming needs, there has been cumulating evidence that the production of self-touch is associated with emotional regulation and cognitive control. Yet, individuals vary greatly in how often they perform self-touch in conversations. The present study investigated how individuals’ anxiety levels (i.e., state and trait anxiety), personality traits (i.e., neuroticism, agreeableness, extraversion, conscientiousness, and openness), and inhibition ability can contribute to the individual differences in conversational self-touch frequency. Spontaneous self-touch was elicited from a hundred and twenty-seven participants in an animated cartoon description task and a social dilemma-solving task. Results from the correlational analysis showed that the self-touch frequency was significantly positively related to individuals’ state and trait anxiety levels and their neuroticism scores but was significantly negatively related to their agreeableness scores. However, when all predictor variables were entered simultaneously into a multiple regression analysis, the result showed that the state anxiety score was the only significant predictor of the conversational self-touch frequency. This result is consistent with the proposal that self-touch behaviors are produced to regulate negative emotional states such as anxiety and stress. The findings of the present study shed new light on the function of self-touch behaviors in conversations, and highlight the importance of using a broad correlational approach with simultaneous consideration of multiple predictors in future research aiming to understand individual differences in self-touch behaviors.

Topical Capsaicin in Poly(lactic-co-glycolic)acid (PLGA) Nanoparticles Decreases Acute Itch and Heat Pain.

Background: Capsaicin, the hot pepper agent, produces burning followed by desensitization. To treat localized itch or pain with minimal burning, low capsaicin concentrations can be repeatedly applied. We hypothesized that alternatively controlled release of capsaicin from poly(lactic-co-glycolic acid) (PLGA) nanoparticles desensitizes superficially terminating nociceptors, reducing burning. Methods: Capsaicin-loaded PLGA nanoparticles were prepared (single-emulsion solvent evaporation) and characterized (size, morphology, capsaicin loading, encapsulation efficiency, in vitro release profile). Capsaicin-PLGA nanoparticles were applied to murine skin and evaluated in healthy human participants (n = 21) for 4 days under blinded conditions, and itch and nociceptive sensations evoked by mechanical, heat stimuli and pruritogens cowhage, β-alanine, BAM8-22 and histamine were evaluated. Results: Nanoparticles (loading: 58 µg capsaicin/mg) released in vitro 23% capsaicin within the first hour and had complete release at 72 h. In mice, 24 h post-application Capsaicin-PLGA nanoparticles penetrated the dermis and led to decreased nociceptive behavioral responses to heat and mechanical stimulation (desensitization). Application in humans produced a weak to moderate burning, dissipating after 3 h. A loss of heat pain up to 2 weeks was observed. After capsaicin nanoparticles, itch and nociceptive sensations were reduced in response to pruritogens cowhage, β-alanine or BAM8-22, but were normal to histamine. Conclusions: Capsaicin nanoparticles could be useful in reducing pain and itch associated with pruritic diseases that are histamine-independent.

Peripheral Neuro-immune Interactions in Atopic Dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disease, characterized by clinical manifestations of dry skin, chronic eczema and severe itching, often combined with asthma and allergic rhinitis. AD can affect as many as 20% of children and 1–3% of adults. Skin barrier dysfunction, inflammatory and immunological abnormalities have long been noted in patients with AD. However, conflicting evidence suggests that enhanced innervation of sensory neurons may contribute to disease pathology in AD. To better understand this phenomenon, we investigated the role of sensory neurons and their relationship with mast cells in itch sensations at different ages of AD initiation. AD was induced by epicutaneous exposure of extracts from Aspergillus fumigatus (ASP) in a sensory neuron reporter animal (Pirt;tdTomato) initiated either at postnatal day14 (P14) or P35. Mice were exposed to ASP extract (or saline) for 3 weeks via patches on the back skin. We performed immunohistochemistry on back skin for mast cell protease 6 (MCPT-6), assessed trans-epidermal water loss (TEWL), and determined scratching behaviors using an artificial intelligence system. We demonstrated an increased total innervation in the skin of ASP treated mice started at P35 but not at P14. There was significant increase in TEWL and thickness of epidermal layers in both AD groups. However, increased thickening at P35 was 2x greater than that observed at P14. This resulted in decreased sensory innervation density specifically in the epidermal layer at P35. We also found increased MCs at the epidermal/dermal border in both ASP treated groups. Surprisingly, ASP treated mice at P14 did not develop robust scratching behaviors as observed at P35. Results suggest that distinctions in innervation density in the epidermis vs dermis in association with MCs may underlie scratching behaviors that contribute to AD progression and could reveal novel treatment strategies for AD. Grant support from 5U19 AI70235-15 R01NS105715 R01NS113965.

IL-20 promotes cutaneous inflammation and peripheral itch sensation in atopic dermatitis.

Atopic dermatitis (AD) is a chronic skin disease, which is associated with intense itch, skin barrier dysfunction and eczematous lesions. Aberrant IL‐20 expression has been implicated in numerous inflammatory diseases, including psoriasis. However, the role of IL‐20 in AD remains unknown. Here, RNA‐seq, Q‐PCR, and immunocytochemistry were utilized to examine disease‐driven changes of IL‐20 and its cognate receptor subunits in skin from healthy human subjects, AD patients and murine AD‐models. Calcium imaging, knockdown and cytokine array were used to investigate IL‐20‐evoked responses in keratinocytes and sensory neurons. The murine cheek model and behavioral scoring were employed to evaluate IL‐20‐elicited sensations in vivo. We found that transcripts and protein of IL‐20 were upregulated in skin from human AD and murine AD‐like models. Topical MC903 treatment in mice ear enhanced IL‐20R1 expression in the trigeminal sensory ganglia, suggesting a lesion‐associated and epidermal‐driven mechanism for sensitization of sensory IL‐20 signaling. IL‐20 triggered calcium influx in both keratinocytes and sensory neurons, and promoted their AD‐related molecule release and transcription of itch‐related genes. In sensory neurons, IL‐20 application increased TLR2 transcripts, implicating a link between innate immune response and IL‐20. In a murine cheek model of acute itch, intradermal injection IL‐20 and IL‐13 elicited significant itch‐like behavior, though only when co‐injected. Our findings provide novel insights into IL‐20 function in peripheral (skin‐derived) itch and clinically relevant intercellular neuron‐epidermal communication, highlighting a role of IL‐20 signaling in the pathophysiology of AD, thus forming a new basis for the development of a novel antipruritic strategy via interrupting IL‐20 epidermal pathways.

Punctate Administration of Ficin as a human and animal model of non-histaminergic itch.

Ficin, a cysteine protease derived from fig-tree latex, has been reported to elicit itch and nociceptive sensations, though quantitative sensory studies are lacking. Cowhage containing the pruritic cysteine Mucunain, on the contrary, has been widely studied as activating polymodal nociceptors and eliciting a histamine-independent itch. We tested whether ficin in heat-inactivated cowhage spicules would elicit itch and nociceptive sensations in humans, and analogous behaviours in mice, which are similar to those evoked by native cowhage, and whether these behaviours in mice were dose-dependent when ficin was injected intradermally. Human volunteers rated the magnitude of itch and nociceptive sensations evoked by either native cowhage spicules or heat-inactivated spicules soaked in 1, 10 or 100 mg/mL ficin (0.03, 0.3 and 3 ng of ficin in spicule tip), applied to forearm. In mice, itch-like scratching and nociceptive-like wiping were recorded in response to either native cowhage, to heat-inactivated spicules that were either inactive or contained 100 mg/mL ficin, or to intradermal injections of 1.25, 2.5 or 5 μg/ 5 μL, each treatment applied to the cheek. The dose of 100 mg/mL ficin in spicules evoked comparable magnitudes of itch, nociceptive sensations and areas of cutaneous dysesthesia as native cowhage in humans and comparable itch-like scratching and pain-like wiping behaviours in mice. But to elicit similar behaviours when injected intradermally in mice a greater amount of ficin (1.25 μg) was required. Spicule delivery or intradermal injection of ficin elicits behaviours in mice that model itch and nociceptive sensations in humans, suggesting that ficin may be useful in translating mechanistic research on the neural mechanisms of pruritic and nociceptive effects of cysteine proteases between the two species.

A Case Report of Pemphigus foliaceus

We report a case of the rarely seen disease pemphigus foliaceus in a 32-year-old female patient with a past medical history of superficial red raised lesion over the body face associated with itching and burning sensation for the treatment which has taken previously and healed pigmentation. She did not respond to topical steroids, and the condition flared up when oral steroids were tapered. Immunofluorescence biopsy and antibody titers can help establish the diagnosis. We discuss the clinical features, pathophysiology, histology, disease course, and treatment of Pemphigus foliaceus.

The role of PTEN in primary sensory neurons in processing itch and thermal information in mice.

PTEN is known as a tumor suppressor and plays essential roles in brain development. Here, we report that PTEN in primary sensory neurons is involved in processing itch and thermal information in adult mice. Deletion of PTEN in the dorsal root ganglia (DRG) is achieved in adult Drg11-CreER: PTENflox/flox (PTEN CKO) mice with oral administration of tamoxifen, and CKO mice develop pathological itch and elevated itch responses on exposure to various pruritogens. PTEN deletion leads to ectopic expression of TRPV1 and MrgprA3 in IB4+ non-peptidergic DRG neurons, and the TRPV1 is responsive to capsaicin. Importantly, the elevated itch responses are no longer present in Drg11-CreER: PTENflox/flox: TRPV1flox/flox (PTEN: TRPV1 dCKO) mice. In addition, thermal stimulation is enhanced in PTEN CKO mice but blunted in dCKO mice. PTEN-involved regulation of itch-related gene expression in DRG neurons provides insights for understanding molecular mechanism of itch and thermal sensation at the spinal level.

Slick Potassium Channels Control Pain and Itch in Distinct Populations of Sensory and Spinal Neurons in Mice

Slick, a sodium-activated potassium channel, has been recently identified in somatosensory pathways, but its functional role is poorly understood. The authors of this study hypothesized that Slick is involved in processing sensations of pain and itch. Immunostaining, in situ hybridization, Western blot, and real-time quantitative reverse transcription polymerase chain reaction were used to investigate the expression of Slick in dorsal root ganglia and the spinal cord. Mice lacking Slick globally (Slick-/-) or conditionally in neurons of the spinal dorsal horn (Lbx1-Slick-/-) were assessed in behavioral models. The authors found Slick to be enriched in nociceptive Aδ-fibers and in populations of interneurons in the spinal dorsal horn. Slick-/- mice, but not Lbx1-Slick-/- mice, showed enhanced responses to noxious heat in the hot plate and tail-immersion tests. Both Slick-/- and Lbx1-Slick-/- mice demonstrated prolonged paw licking after capsaicin injection (mean ± SD, 45.6 ± 30.1 s [95% CI, 19.8 to 71.4]; and 13.1 ± 16.1 s [95% CI, 1.8 to 28.0]; P = 0.006 [Slick-/- {n = 8} and wild-type {n = 7}, respectively]), which was paralleled by increased phosphorylation of the neuronal activity marker extracellular signal-regulated kinase in the spinal cord. In the spinal dorsal horn, Slick is colocalized with somatostatin receptor 2 (SSTR2), and intrathecal preadministration of the SSTR2 antagonist CYN-154806 prevented increased capsaicin-induced licking in Slick-/- and Lbx1-Slick-/- mice. Moreover, scratching after intrathecal delivery of the somatostatin analog octreotide was considerably reduced in Slick-/- and Lbx1-Slick-/- mice (Slick-/- [n = 8]: 6.1 ± 6.7 bouts [95% CI, 0.6 to 11.7]; wild-type [n =8]: 47.4 ± 51.1 bouts [95% CI, 4.8 to 90.2]; P = 0.039). Slick expressed in a subset of sensory neurons modulates heat-induced pain, while Slick expressed in spinal cord interneurons inhibits capsaicin-induced pain but facilitates somatostatin-induced itch.

Pruritus: A Sensory Symptom Generated in Cutaneous Immuno-Neuronal Crosstalk.

Pruritus or itch generated in the skin is one of the most widespread symptoms associated with various dermatological and systemic (immunological) conditions. Although many details about the molecular mechanisms of the development of both acute and chronic itch were uncovered in the last 2 decades, our understanding is still incomplete and the clinical management of pruritic conditions is one of the biggest challenges in daily dermatological practice. Recent research revealed molecular interactions between pruriceptive sensory neurons and surrounding cutaneous cell types including keratinocytes, as well as resident and transient cells of innate and adaptive immunity. Especially in inflammatory conditions, these cutaneous cells can produce various mediators, which can contribute to the excitation of pruriceptive sensory fibers resulting in itch sensation. There also exists significant communication in the opposite direction: sensory neurons can release mediators that maintain an inflamed, pruritic tissue-environment. In this review, we summarize the current knowledge about the sensory transduction of pruritus detailing the local intercellular interactions that generate itch. We especially emphasize the role of various pruritic mediators in the bidirectional crosstalk between cutaneous non-neuronal cells and sensory fibers. We also list various dermatoses and immunological conditions associated with itch, and discuss the potential immune-neuronal interactions promoting the development of pruritus in the particular diseases. These data may unveil putative new targets for antipruritic pharmacological interventions.

The emerging role of the neuroimmune cytokine interleukin-31 in chronic inflammatory skin diseases.

Chronic inflammatory skin diseases pose significant challenges for both patients and clinicians worldwide. Atopic dermatitis (AD), the most common of these diseases, affects up to 8% of the adult population depending on geographic location and demographic group, while prurigo nodularis (PN) is a less common disease that causes significant burden. In these inflammatory skin conditions, pruritus is a cardinal symptom. Interleukin 31 (IL-31), described as a neuroimmune modulator, has been shown to have a prominent role in both inflammation and itch. IL-31 acts through a receptor complex consisting of IL-31 receptor α (IL-31RA) and oncostatin M receptor β (OSMRβ). IL-31 is produced by a variety of cells, including type 2 helper T cells, and IL-31 signaling can activate three important pathways: JAK/STAT, P13K/AKT, and ERK/MAPK. IL-31 is elevated in AD and PN, and is thought to induce chemokine genes CCL1, CCL17, and CCL22. The chemokines recruit T cells to affected skin, where more IL-31 is secreted. The IL-31 receptor complex is also abundant in dorsal root ganglia in human tissue, home of primary sensory neurons and the distal source of "itch sensations." IL-31 and its receptor complex have an important role in chronic inflammatory diseases, including AD and PN, and blocking the IL-31/IL-31RA signaling may represent an important new therapeutic approach for these diseases, which continue to have significant unmet medical needs.

MANAGEMENT OF PRESSURE URTICARIA (SHĪTPITTA) THROUGH VIRECANA : A CASE REPORT

Introduction: A 32 years old female patient consulted for the following complaints- frequent episodes of papular, pinkish red rashes on whole body on applying pressure or scratching, associated with marked itching and burning sensation since one and a half month. She was clinically diagnosed as acute case of Shītpitta that can be correlated with urticaria (pressure urticaria: due to pressure). Material and Methods: Ayurvedic Śodhana (Virecana) and Śamana treatment were used to successfully manage this condition. The goal of this case study is to illustrate how Śodhana (bio-purication treatments) and Śamana (palliative) therapy might be benecial in the treatment of allergic disorders such as urticaria. Result and Conclusion: After receiving Virecana and oral medication, the patient's symptoms considerably improved. Although contemporary medicine offers a variety of treatment options for urticaria and other allergic skin conditions, recurrence is typical even after medication. This case study shown that Ayurvedic management (Virecana as Śodhana therapy and Śamana āusadha) may be useful in the treatment of skin issues.

EFFECT OF GANDHAKA TAILA ON PAMA (SCABIES)

In the present clinical study we observed in majority (75%) of patients where use of Gandhaka taila as external application in Pama markedly reduced itching, lessions, oozing and burning sensation.

Scalp dysesthesia: a neuropathic phenomenon.

Scalp dysesthesia is an abnormal sensation of the scalp in the absence of cutaneous disease. It is characterized by a burning and/or itching sensation and can be related to a variety of neurogenic or psychogenic causes. This condition is extremely bothersome and is also common- especially among the geriatric population, in women, in patients with diabetes mellitus, and patients with psychiatric history. However, despite its prevalence in many populations, there are limited data about its causes and characteristics. Given its limited cutaneous manifestations, it is also easily misdiagnosed and an underrecognized cause of scalp pruritus in the dermatological community. Therefore, education on scalp dysesthesia is paramount to helping physicians identify and provide appropriate treatment for these patients. This review focuses predominantly on the neurogenic causes (with a brief review of psychogenic itch) of scalp dysesthesia and the therapeutics that have been found to be effective for this condition. Neurogenic causes of scalp dysesthesia occur with damage to the central or peripheral pathways of itch sensation, resulting in modification and heightened sensitivity of nerves that result in abnormal sensations in the absence of or out of proportion to external stimuli. A comprehensive review of etiologies is provided here, ranging from lesions to the central nervous system caused by cervical spine disease, trigeminal trophic syndrome, tumor, stroke, and multiple sclerosis, to small-fiber neuropathies caused by diabetes, brow lifts, keloid, and burn scarring. Recently, there have also been reports of scalp dysesthesias associated with post-infectious COVID-19. Treatment options tailored toward disease severity and different causes of disease will also be discussed. By elucidating the different mechanisms and therapeutic treatments of scalp dysesthesia, we hope to provide clinicians with the tools to identify and treat this condition as well as encourage further research into its etiologies and therapeutics.

Scratching the surface of itch receptors

The discovery of Mas-related G protein-coupled receptors (MRGPRs) in itch sensation promised a search for novel therapeutics of itch that ultimately met with little success. Recent structural determination of these receptors by Roth and Sun marks a big step forward in the search for therapeutics of debilitating itch.