Leigh A. Nattkemper

Brain's reward circuits mediate itch relief. a functional MRI study of active scratching.

Previous brain imaging studies investigating the brain processing of scratching used an exogenous intervention mimicking scratching, performed not by the subjects themselves, but delivered by an investigator. In real life, scratching is a conscious, voluntary, controlled motor response to itching, which is directed to the perceived site of distress. In this study we aimed to visualize in real-time by brain imaging the core mechanisms of the itch-scratch cycle when scratching was performed by subjects themselves. Secondly, we aimed to assess the correlations between brain patterns of activation and psychophysical ratings of itch relief or pleasurability of scratching. We also compared the patterns of brain activity evoked by self-scratching vs. passive scratching. We used a robust tridimensional Arterial Spin Labeling fMRI technique that is less sensitive to motion artifacts: 3D gradient echo and spin echo (GRASE) - Propeller. Active scratching was accompanied by a higher pleasurability and induced a more pronounced deactivation of the anterior cingulate cortex and insula, in comparison with passive scratching. A significant involvement of the reward system including the ventral tegmentum of the midbrain, coupled with a mechanism deactivating the periaqueductal gray matter (PAG), suggests that itch modulation operates in reverse to the mechanism known to suppress pain. Our findings not only confirm a role for the central networks processing reward in the pleasurable aspects of scratching, but also suggest they play a role in mediating itch relief.

Itch Prevalence and Characteristics in a Hispanic Geriatric Population: A Comprehensive Study Using a Standardized Itch Questionnaire

A cross-sectional study of geriatric patients was performed to provide a comprehensive description of the prevalence and clinical characteristics of chronic itch affecting Hispanic geriatric subjects in Mexico. Participants were recruited from both nursing homes and geriatric ambulatory care centers. Patients without dementia were evaluated using an itch intensity and characteristic questionnaire and were assessed for itch-related dermatoses (n = 302). Data on medications and underlying systemic diseases were obtained from medical records. The prevalence of chronic itch was 25% in this population. Of those with chronic itch, 69% had xerosis, 28% had itch-related dermatoses, and 96% had documented comorbidities. The most common comorbidities were diabetes mellitus (OR = 2.3, 95% CI 1.3-3.9, p = 0.003) and chronic venous insufficiency (OR = 4.4, 95% CI 1.6-12.2, p = 0.002). The most common areas where patients experienced itch were legs (54%), back (45%), scalp (28%) and arms (27%). Patients experienced the greatest amount of itch in the winter (77%) and during the night (65%). Chronic itch is a common problem in the studied Hispanic geriatric population, and its presence significantly correlates with xerosis, diabetes, and venous insufficiency.

Monkey see, monkey do: contagious itch in nonhuman primates.

Contagious itch has been anecdotally reported and recently confirmed in a controlled setting in humans. Here, we investigated in adult rhesus macaques whether contagious itch occurs spontaneously in monkeys. In a first experiment, the latency to scratch following cage-mate scratching was observed in pair-housed adult rhesus macaques. Scratching increased within the first 60 s and subsequently declined. In a second experiment, scratching behavior was recorded for individually caged adult rhesus macaques which where shown videos of monkeys scratching, but also neutral stimuli. A greater frequency of scratching was observed when monkeys viewed a video sequence of another monkey scratching as well as during the neutral stimulus immediately following the monkey scratching segment. In conclusion, viewing other monkeys scratching significantly increased scratching behavior in adult rhesus macaques.

A study of serum concentrations and dermal levels of NGF in atopic dermatitis and healthy subjects

Nerve growth factor (NGF) was reported to be increased in the serum and skin of atopic dermatitis (AD) patients, to the extent that serum nerve growth factor levels were proposed to serve as a marker of disease severity. We studied NGF levels in the serum and dermis using skin microdialysis and attempted to correlate them with disease severity. We also examined if potential differences between morning and evening levels of NGF can explain the phenomenon of nocturnal itch. In addition, neurogenic inflammation and itch were induced using histamine iontophoresis in lesional and non-lesional skin and the effect of experimental itch on dermal NGF concentration was examined. We found that systemic (serum) and eczematous skin levels of NGF in AD are significantly lower in comparison to healthy controls. Serum NGF decreases from morning to late afternoon in both groups. Interestingly, serum NGF levels were correlated to disease severity in the morning in AD, although the NGF concentration in AD were significantly lower than in the healthy group. The local itch and neurogenic inflammation induction via experimental histamine reduced local NGF levels in the eczema and non-lesional skin in atopics, but not in the healthy controls, where it was slightly increased. The higher the clinical severity of the eczema, a significantly less pronounced effect of neurogenic inflammation on the local levels of NGF was found. The availability of measurable NGF might be reduced by a higher expression of NGF receptors. The fluctuations of NGF levels during the day suggest a complex modulation of this neurotrophin, potentially linked to stress or to an altered neurophysiological mechanism.

Overexpression of the gastrin-releasing peptide in cutaneous nerve fibers and its receptor in the spinal cord in primates with chronic itch.

Leigh A. Nattkemper1,2, Zhong-Qiu Zhao5, Anna J. Nichols6, Alexandru D.P. Papoiu1, Carol A. Shively4, Zhou-Feng Chen5, and Gil Yosipovitch1,2,3,* 1Department of Dermatology, Wake Forest University School of Medicine, Winston Salem, NC, USA 2Department of Neurobiology & Anatomy, University Wake Forest School of Medicine, Winston Salem, NC, USA 3Department of Regenerative Medicine, Wake Forest University School of Medicine, Winston Salem, NC, USA 4Department of Comparative Medicine, Wake Forest University School of Medicine, Winston Salem, NC, USA 5Center for the Study of Itch, Washington University School of Medicine, St. Louis, MO, USA 6Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA

Psychological Stress and Skin Symptoms in College Students: Results of a Cross-sectional Web-based Questionnaire Study.

OR and 95% confidence intervals were calculated to conclude as to whether the low stress group had a lower probability of having (skin-) complaints than the high stress group. Due to the fact that sex was not equally distributed in the groups, sex and stress severity were used as a covariate in the binary logistic regressions which were subsequently conducted using the skin symptoms as dependent variables. This made it possible to report OR and 95% confidence intervals (CI) adjusted for sex.

The prevalence and characteristics of chronic ocular itch: a cross-sectional survey

Introduction: In this cross-sectional study, we aimed to determine the prevalence and characteristics of chronic ocular itch in an outpatient ophthalmology and optometry clinic. Methods: Four hundred patients from an outpatient ophthalmology and optometry clinic were enrolled. The presence and characteristics of chronic ocular itch were assessed by a questionnaire. Data regarding ophthalmologic, dermatologic, and systemic conditions as well as current medications were extracted from medical records. Results: Chronic ocular itch was present in 118 (29.5%) of 400 participants. Chronic ocular pruritus was significantly more prevalent in females [P=0.015; odds ratio (OR)=1.8; 95% confidence interval (CI), 1.1–2.8] and was significantly associated with the presence of allergic conjunctivitis [51.8% (n=45); P<0.001; OR=5.0; 95% CI, 3.0–8.3], dry eye syndrome [40.1% (75); P<0.001; OR=2.6; 95% CI, 1.7–4.1], blepharitis [43.8% (n=21); P=0.021; OR=2.0; 95% CI, 1.1–3.8], and atopic dermatitis [50.0% (n=10); P=0.023; OR=2.6; 95% CI, 1.1–5.8]. Chronic ocular itch was not significantly associated with systemic conditions, or the use of prescribed ophthalmologic medications. Discussion: Chronic ocular itch is common and may be related to ophthalmologic or dermatologic pathologies. The present findings highlight the importance of identifying and managing this uncomfortable symptom that may negatively impact the quality of life and sleep of affected patients.

Suppression of scratching-induced pleasurable sensation by compression nerve blocking and its association with itch relief

Itch can be suppressed by scratching. At the same time, scratching evokes a pleasurable sensation. In the present study, we investigated the peripheral mechanism of scratching-induced pleasurability and its association with itch relief using compression nerve block. We found that myelinated nerve fibers (A&bgr;-fibers and possibly A&dgr;-fibers), are involved in transmission of scratching-induced pleasurability. We observed that itch relief effect was the same regardless of whether the pleasurable sensation was evoked by scratching an itch, indicating that pleasure is not a necessary component to induce itch relief. This is the first study to investigate the peripheral mechanism of scratching-induced pleasurability and itch relief.

Expression of Histidine Decarboxylase in the Epidermis of Primates with Chronic Itch

Chronic itch is a burdensome clinical issue that has a significant negative impact on quality of life. In the past two decades, the volume of research on itch has increased immensely. However, there is still a significant lack of translation from scientific findings into medical practice. We previously identified a colony of Cynomolgus macaques (Macaca fascicularis) suffering from idiopathic chronic itch (1). This non-human primate chronic itch model could provide a translational bridge for studying chronic itch. Histidine decarboxylase (HDC) is the enzyme that catalyzes the synthesis of histamine. Recently, an increase in epidermal HDC was shown in acute and chronic itch-related behaviors induced by topical application of anionic surfactants in mice (2, 3). Additionally, epidermal HDC is elevated in mice with α-melanocyte-stimulating hormone-induced itch (4). Thus, these findings suggest that increased HDC in the epidermis might play a role in itch. In the present study, we investigated whether epidermal HDC is associated with itch severity in the primate model.