Electrically Evoked Itch in Human Subjects

Solinski, Hans Jürgen; Rukwied, Roman

doi:10.3389/fmed.2020.627617

Cited by 5 publications

(8 citation statements)

References 85 publications

(129 reference statements)

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“…No matter which of the transmission theories for itch proves ultimately true, itch, like pain (Fillingim, 2017 ), exhibits large interindividual variability, as observed with human subjects and atopic dermatitis patients: in this study, individual differences in skin pathophysiology and psychological state were suggested as possible reasons for the observed differences (Solinski and Rukwied, 2020 ). Further examples are provided based on the side effects of specific drugs.…”

Section: Introductionmentioning

confidence: 67%

Generalized resistance to pruritogen-induced scratching in the C3H/HeJ strain

Zhang

Richter

König

et al. 2022

Front. Mol. Neurosci.

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Previously the effect of the pruritogens, such as histamine and chloroquine, was tested in 11 inbred mouse strains, and this study aimed to identify resistant and sensitive strains, consistent with the observation that underlies the large variability in human populations. In the present study, we used the low responder C3H/HeJ (C3H) and the more sensitive C57BL/6J (C57) strain to find out if resistance and sensitivity to develop pruritus is restricted to only histamine and chloroquine or extends to other known pruritogens as well. We tested five additional commonly known pruritogens. We established dose-response relationships by injecting four concentrations of the pruritogens in the range of 0.3, 1, 3, and ten-fold in the nuchal fold. Then we assessed the scratching behavior for 30 min after injection with an automated custom-designed device based on the bilateral implantation of mini-magnets in the hind paws and on single cages placed within a magnetic coil. We found that the resistance to pruritogens is a general phenotype of the C3H strain and extends to all pruritogens tested, including not only histamine and chloroquine, but also endothelin, trypsin, 5-HT (serotonin), the short peptide SLIGRL, and Lysophosphatidic acid (LPA). C57 was more sensitive to all pruritogens and, in contrast to C3H, dose-response relationships were evident for some of the pruritogens. In general, comparable peak scratch responses were observed for the 0.3-fold concentrations of the pruritogens in C57 whereas C3H required at least the ten-fold concentration and still displayed only between 5 and 33% of the scratch responses observed in C57 for the respective pruritogen. The general resistance to pruritogens and the low level of scratching behavior found in the C3H strain is an interesting trait and represents a model for the study of the heritability of itch. It is accompanied in C3H with a higher sensitivity in assays of nociception.

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Section: Introductionmentioning

confidence: 67%

Generalized resistance to pruritogen-induced scratching in the C3H/HeJ strain

Zhang

Richter

König

et al. 2022

Front. Mol. Neurosci.

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“…Other studies have evoked cutaneous itch electrically and thereby gained better temporal control on pruritus generation without allergen sensitization or dependence on chemical pathways ( Solinski and Rukwied, 2020 ). However, this mechanism without pruritogen receptor activation is perhaps best suited to observe brain activity patterns and to identify regions involved in itch processing.…”

Section: State Of the Art In Itch Researchmentioning

confidence: 99%

In vitro models for investigating itch

Mießner

Seidel²,

Smith³

2022

Front. Mol. Neurosci.

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Itch (pruritus) is a sensation that drives a desire to scratch, a behavior observed in many animals. Although generally short-lasting and not causing harm, there are several pathological conditions where chronic itch is a hallmark symptom and in which prolonged scratching can induce damage. Finding medications to counteract the sensation of chronic itch has proven difficult due to the molecular complexity that involves a multitude of triggers, receptors and signaling pathways between skin, immune and nerve cells. While much has been learned about pruritus from in vivo animal models, they have limitations that corroborate the necessity for a transition to more human disease-like models. Also, reducing animal use should be encouraged in research. However, conducting human in vivo experiments can also be ethically challenging. Thus, there is a clear need for surrogate models to be used in pre-clinical investigation of the mechanisms of itch. Most in vitro models used for itch research focus on the use of known pruritogens. For this, sensory neurons and different types of skin and/or immune cells are stimulated in 2D or 3D co-culture, and factors such as neurotransmitter or cytokine release can be measured. There are however limitations of such simplistic in vitro models. For example, not all naturally occurring cell types are present and there is also no connection to the itch-sensing organ, the central nervous system (CNS). Nevertheless, in vitro models offer a chance to investigate otherwise inaccessible specific cell–cell interactions and molecular pathways. In recent years, stem cell-based approaches and human primary cells have emerged as viable alternatives to standard cell lines or animal tissue. As in vitro models have increased in their complexity, further opportunities for more elaborated means of investigating itch have been developed. In this review, we introduce the latest concepts of itch and discuss the advantages and limitations of current in vitro models, which provide valuable contributions to pruritus research and might help to meet the unmet clinical need for more refined anti-pruritic substances.

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“…1 In this process, the neurosensory signal is conducted by primary afferent fibers (pruriceptors) from the skin chemical (e.g., pH), physical (e.g., temperature, tissue tension), and cellular (e.g., lymphocytes, macrophages) environmental conditions. [6][7][8] Of particular interest is the influence of pruriceptors and thermosensitive nociceptors on sensory neurons (thermoceptors). The latter include both cold (activity <35 • C) and heat (activity >25 • C/>35 • C) receptors.…”

Section: Introductionmentioning

confidence: 99%

“…These pseudounipolar and polymodal pruriceptors are divided according to biophysical criteria into thin myelinated A (diameter 2–5 μm, conduction velocity < 8 m/s) and unmyelinated C fibers (diameter 0.2–1.5 μm, conduction velocity < 2 m/s) 4,5 . They are integrated into an interactive milieu that is regulated and determined by molecular (e.g., cytokines, ion channels), chemical (e.g., pH), physical (e.g., temperature, tissue tension), and cellular (e.g., lymphocytes, macrophages) environmental conditions 6–8 . Of particular interest is the influence of pruriceptors and thermosensitive nociceptors on sensory neurons (thermoceptors).…”

Section: Introductionmentioning

confidence: 99%

Efficiency of cutaneous heat diffusion after local hyperthermia for the treatment of itch

Wohlrab

Mentel²,

Eichner

2023

Skin Research and Technology

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Background Today, itching is understood as an independent sensory perception, which is based on a complex etiology of a disturbed neuronal activity and leads to clinical symptoms. The primary afferents (pruriceptors) have functional overlaps with afferents of thermoregulation (thermoceptors). Thus, an antipruritic effect can be caused by antagonizing heat‐sensitive receptors of the skin. The ion channel TRP‐subfamily V member 1 (TRPV1) is of particular importance in this context. Repeated heat application can induce irreversible inactivation by unfolding of the protein, causing a persistent functional deficit and thus clinically and therapeutically reducing itch sensation. Material and methods To demonstrate relevant heat diffusion after local application of heat (45°C to 52°C for 3 and 5 seconds) by a technical medical device, the temperature profile for the relevant skin layer was recorded synchronously on ex vivo human skin using an infrared microscope. Results The results showed that the necessary activation temperature for TRPV1 of (≥43°C) in the upper relevant skin layers was safely reached after 3 and 5 seconds of application time. There were no indications of undesirable thermal effects. Conclusion The test results show that the objectified performance of the investigated medical device can be expected to provide the necessary temperature input for the activation of heat‐sensitive receptors in the skin. Clinical studies are necessary to prove therapeutic efficacy in the indication pruritus.

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Electrically Evoked Itch in Human Subjects

Cited by 5 publications

References 85 publications

Generalized resistance to pruritogen-induced scratching in the C3H/HeJ strain

Generalized resistance to pruritogen-induced scratching in the C3H/HeJ strain

In vitro models for investigating itch

Efficiency of cutaneous heat diffusion after local hyperthermia for the treatment of itch

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