Brain processing of contagious itch in patients with atopic dermatitis

Several studies show that itch and scratching cannot only be induced by pruritogens like histamine or cowhage, but also by the presentation of certain (audio-) visual stimuli like pictures on crawling insects or videos showing other people scratching. This phenomenon is coined Contagious itch (CI). Due to the fact that CI is more profound in patients with the chronic itchy skin disease atopic dermatitis (AD), we believe that it is highly relevant to study brain processing of CI in this group. Knowledge on brain areas involved in CI in AD-patients can provide us with useful hints regarding non-invasive treatments that AD-patients could profit from when they are confronted with itch-inducing situations in daily life. Therefore, this study investigated the brain processing of CI in AD-patients. 11 AD-patients underwent fMRI scans during the presentation of an itch inducing experimental video (EV) and a non-itch inducing control video (CV). Perfusion based brain activity was measured using arterial spin labeling functional MRI. As expected, the EV compared to the CV led to an increase in itch and scratching (p \u3c 0.05). CI led to a significant increase in brain activity in the supplementary motor area, left ventral striatum and right orbitofrontal cortex (threshold: p \u3c 0.001; cluster size k \u3e 50). Moreover, itch induced by watching the EV was by trend correlated with activity in memory-related regions including the temporal cortex and the (pre-) cuneus as well as the posterior operculum, a brain region involved in itch processing (threshold: p \u3c 0.005; cluster size k \u3e 50). These findings suggest that the fronto-striatal circuit, which is associated with the desire to scratch, might be a target region for non-invasive treatments in AD patients. © 2017 Schut, Mochizuki, Grossman, Lin, Conklin, Mohamed, Gieler, Kupfer and Yosipovitch

Cowhage-Induced Itch as an Experimental Model for Pruritus. A Comparative Study with Histamine-Induced Itch

Histamine is the prototypical pruritogen used in experimental itch induction. However, in most chronic pruritic diseases, itch is not predominantly mediated by histamine. Cowhage-induced itch, on the other hand, seems more characteristic of itch occurring in chronic pruritic diseases.We tested the validity of cowhage as an itch-inducing agent by contrasting it with the classical itch inducer, histamine, in healthy subjects and atopic dermatitis (AD) patients. We also investigated whether there was a cumulative effect when both agents were combined.Fifteen healthy individuals and fifteen AD patients were recruited. Experimental itch induction was performed in eczema-free areas on the volar aspects of the forearm, using different itch inducers: histamine, cowhage and their combination thereof. Itch intensity was assessed continuously for 5.5 minutes after stimulus application using a computer-assisted visual analogue scale (COVAS).In both healthy and AD subjects, the mean and peak intensity of itch were higher after the application of cowhage compared to histamine, and were higher after the combined application of cowhage and histamine, compared to histamine alone (p<0.0001 in all cases). Itch intensity ratings were not significantly different between healthy and AD subjects for the same itch inducer used; however AD subjects exhibited a prolonged itch response in comparison to healthy subjects (p<0.001).Cowhage induced a more intense itch sensation compared to histamine. Cowhage was the dominant factor in itch perception when both pathways were stimulated in the same time. Cowhage-induced itch is a suitable model for the study of itch in AD and other chronic pruritic diseases, and it can serve as a new model for testing antipruritic drugs in humans

Cellular, circuit and transcriptional framework for modulation of itch in the central amygdala

Itch is an unpleasant sensation that elicits robust scratching and aversive experience. However, the identity of the cells and neural circuits that organize this information remains elusive. Here, we show the necessity and sufficiency of chloroquine-activated neurons in the central amygdala (CeA) for both itch sensation and associated aversion. Further, we show that chloroquine-activated CeA neurons play important roles in itch-related comorbidities, including anxiety-like behaviors, but not in some aversive and appetitive behaviors previously ascribed to CeA neurons. RNA-sequencing of chloroquine-activated CeA neurons identified several differentially expressed genes as well as potential key signaling pathways in regulating pruritis. Finally, viral tracing experiments demonstrate that these neurons send projections to the ventral periaqueductal gray that are critical in modulation of itch. These findings reveal a cellular and circuit signature of CeA neurons orchestrating behavioral and affective responses to pruritus in mice

Somatosensory pleasure circuit: From skin to brain and back

The skin senses serve a discriminative function, allowing us to manipulate objects and detect touch and temperature, and an affective/emotional function, manifested as itch or pain when the skin is damaged. Two different classes of nerve fibre mediate these dissociable aspects of cutaneous somatosensation: (i) myelinated A-beta and A-delta afferents that provide rapid information about the location and physical characteristics of skin contact; and (ii) unmyelinated, slow-conducting C-fibre afferents that are typically associated with coding the emotional properties of pain and itch. However, recent research has identified a third class of C-fibre afferents that code for the pleasurable properties of touch - c-tactile afferents or CTs. Clinical application of treatments that target pleasant, CT-mediated touch (such as massage therapy) could, in the future, provide a complementary, non-pharmacological means of treating both the physical and psychological aspects of chronic skin conditions such as itch and eczema

Are sex and history of pruritic skin conditions factors which affect the phenomenon of visually evoked itch? An exploratory study

Introduction: We have previously shown that sensations of itch and the scratch response can be evoked using itch-related images. However, we did not determine whether individual differences in a person’s experience of itch could moderate this effect. This exploratory study aimed to determine whether sex or a history of pruritic skin conditions (PSCs) could influence the effects of visually evoked itch and scratch. Methods: Forty-one participants (19 males; 16 with a history of PSCs) viewed static images that could either be itch or nonitch related. These were further separated by picture type: “skin contact” (ants crawling on the hand vs. a butterfly on the finger); “skin response” (scratching an insect bite vs. washing the hands); “skin condition” (psoriasis vs. freckles) or “context only” (insects vs. birds). Images were rated using a 10-point scale by answering: “How itchy do you feel?” (Self-rating) and “How itchy do you think the person in the picture feels?” (Other-rating). Frequency and location of scratching was also recorded. Results: The highest itch scores were to itch-related skin contact pictures. Females gave higher itch ratings than males, and people with a history of PSCs gave higher itch ratings when viewing images of people scratching. There was no correlation between itch ratings and scratch response, and no relationship between body site viewed and location of scratching. Discussion: There is a heightened response to itch-related cues in females and those with PSCs, indicating a more centrally mediated pathway bringing subconscious itch sensations into conscious awareness in these populations. These findings could influence personalized treatment interventions aimed at reducing awareness of itch sensations in susceptible individuals

Neural correlates of self-injurious behavior in Prader-Willi syndrome

Individuals with Prader–Willi syndrome (PWS), a genetic disorder caused by mutations to the q11‐13 region on chromosome 15, commonly show severe skin‐picking behaviors that can cause open wounds and sores on the body. To our knowledge, however, no studies have examined the potential neural mechanisms underlying these behaviors. Seventeen individuals with PWS, aged 6–25 years, who showed severe skin‐picking behaviors, were recruited and scanned on a 3T scanner. We used functional magnetic resonance imaging (fMRI) while episodes of skin picking were recorded on an MRI‐safe video camera. Three participants displayed skin picking continuously throughout the scan, three participants did not display skin picking, and the data for one participant evidenced significant B0 inhomogeneity that could not be corrected. The data for the remaining 10 participants (six male, four female) who displayed a sufficient number of picking and nonpicking episodes were subjected to fMRI analysis. Results showed that regions involved in interoceptive, motor, attention, and somatosensory processing were activated during episodes of skin‐picking behavior compared with nonpicking episodes. Scores obtained on the Self‐Injury Trauma scale were significantly negatively correlated with mean activation within the right insula and left precentral gyrus. These data indicate that itch and pain processes appear to underlie skin‐picking behaviors in PWS, suggesting that interoceptive disturbance may contribute to the severity and maintenance of abnormal skin‐picking behaviors in PWS. Implications for treatments are discussed. Hum Brain Mapp 36:4135–4143, 2015

Neural correlates of evidence accumulation during value-based decisions revealed via simultaneous EEG-fMRI

Current computational accounts posit that, in simple binary choices, humans accumulate evidence in favour of the different alternatives before committing to a decision. Neural correlates of this accumulating activity have been found during perceptual decisions in parietal and prefrontal cortex; however the source of such activity in value-based choices remains unknown. Here we use simultaneous EEG–fMRI and computational modelling to identify EEG signals reflecting an accumulation process and demonstrate that the within- and across-trial variability in these signals explains fMRI responses in posterior-medial frontal cortex. Consistent with its role in integrating the evidence prior to reaching a decision, this region also exhibits task-dependent coupling with the ventromedial prefrontal cortex and the striatum, brain areas known to encode the subjective value of the decision alternatives. These results further endorse the proposition of an evidence accumulation process during value-based decisions in humans and implicate the posterior-medial frontal cortex in this process

Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch

Topical capsaicin formulations are used for pain management. Safety and modest efficacy of low-concentration capsaicin formulations, which require repeated daily self-administration, are supported by meta-analyses of numerous studies. A high-concentration capsaicin 8% patch (Qutenza™) was recently approved in the EU and USA. A single 60-min application in patients with neuropathic pain produced effective pain relief for up to 12 weeks. Advantages of the high-concentration capsaicin patch include longer duration of effect, patient compliance, and low risk for systemic effects or drug–drug interactions. The mechanism of action of topical capsaicin has been ascribed to depletion of substance P. However, experimental and clinical studies show that depletion of substance P from nociceptors is only a correlate of capsaicin treatment and has little, if any, causative role in pain relief. Rather, topical capsaicin acts in the skin to attenuate cutaneous hypersensitivity and reduce pain by a process best described as ‘defunctionalization’ of nociceptor fibres. Defunctionalization is due to a number of effects that include temporary loss of membrane potential, inability to transport neurotrophic factors leading to altered phenotype, and reversible retraction of epidermal and dermal nerve fibre terminals. Peripheral neuropathic hypersensitivity is mediated by diverse mechanisms, including altered expression of the capsaicin receptor TRPV1 or other key ion channels in affected or intact adjacent peripheral nociceptive nerve fibres, aberrant re-innervation, and collateral sprouting, all of which are defunctionalized by topical capsaicin. Evidence suggests that the utility of topical capsaicin may extend beyond painful peripheral neuropathies