Merkel cells: A collective review of current concepts

Abraham, Jacob; Mathew, Sherin

doi:10.4103/ijabmr.ijabmr_34_18

Cited by 40 publications

(22 citation statements)

References 59 publications

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“…76 Strikingly, robust EGFP and CB 2 expression was detected on Merkel cells in the SB of the epidermis where they produce neuromodulatory effects on lowthreshold mechanoreceptive Merkel endings supplied by myelinated Ab DRG neurons that might contribute to mechanical allodynia under pathological conditions. 1,30 The increased density of epidermal LCs in various pain conditions 16,18,47 suggests a possible neuroimmune communication between LCs and nerves in the pathogenesis of neuropathy. 51,81 The onset of pain triggered by an increase of LCs occurs by release of nitric oxide, 72 neurotrophic factors, 92 and proinflammatory cytokines, 20,81 resulting in the sensitization of nociceptors and mechanical hypersensitivity.…”

Section: Discussionmentioning

confidence: 99%

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A peripheral CB2 cannabinoid receptor mechanism suppresses chemotherapy-induced peripheral neuropathy: evidence from a CB2 reporter mouse

Lin

Carey

et al. 2021

Pain

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CB 2 cannabinoid receptors (CB 2 ) are a promising therapeutic target that lacks unwanted side effects of CB 1 activation. However, the cell types expressing CB 2 that mediate these effects remain poorly understood. We used transgenic mice with CB 2 promoter-driven expression of enhanced green fluorescent protein (EGFP) to study cell types that express CB 2 and suppress neuropathic nociception in a mouse model of chemotherapy-induced peripheral neuropathy. Structurally distinct CB 2 agonists (AM1710 and LY2828360) suppressed paclitaxel-induced mechanical and cold allodynia in CB 2 EGFP reporter mice with established neuropathy. Antiallodynic effects of AM1710 were blocked by SR144528, a CB 2 antagonist with limited CNS penetration. Intraplantar AM1710 administration suppressed paclitaxel-induced neuropathic nociception in CB 2 EGFP but not CB 2 knockout mice, consistent with a local site of antiallodynic action. mRNA expression levels of the anti-inflammatory cytokine interleukin-10 were elevated in the lumbar spinal cord after intraplantar AM1710 injection along with the proinflammatory cytokine tumor necrosis factor alpha and chemokine monocyte chemoattractant protein-1. CB 2 EGFP , but not wildtype mice, exhibited anti-GFP immunoreactivity in the spleen. However, the anti-GFP signal was below the threshold for detection in the spinal cord and brain of either vehicle-treated or paclitaxel-treated CB 2 EGFP mice. EGFP fluorescence was coexpressed with CB 2 immunolabeling in stratified patterns among epidermal keratinocytes. EGFP fluorescence was also expressed in dendritic cells in the dermis, Langerhans cells in the epidermis, and Merkel cells. Quantification of the EGFP signal revealed that Langerhans cells were dynamically increased in the epidermis after paclitaxel treatment. Our studies implicate CB 2 expressed in previously unrecognized populations of skin cells as a potential target for suppressing chemotherapy-induced neuropathic nociception.

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Section: Discussionmentioning

confidence: 99%

“… 76 Strikingly, robust EGFP and CB 2 expression was detected on Merkel cells in the SB of the epidermis where they produce neuromodulatory effects on low-threshold mechanoreceptive Merkel endings supplied by myelinated Aβ DRG neurons that might contribute to mechanical allodynia under pathological conditions. 1 , 30 …”

Section: Discussionmentioning

confidence: 99%

A peripheral CB2 cannabinoid receptor mechanism suppresses chemotherapy-induced peripheral neuropathy: evidence from a CB2 reporter mouse

Lin

Carey

et al. 2021

Pain

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“…Yet, unilateral investigation of left S1 identified representation patterns associated with aversive pressure in absence of specific touch experience, indicating that discriminative and nociceptive information may be integrated before reaching S1 (for candidate regions, see Abraira et al, 2017 ; Marshall and McGlone, 2020 ; Neubarth et al, 2020 ). Alternatively, it may be that sustained changes in tonic firing of rates of slow adapting mechanoreceptors (for review, see Knibestol, 1975 ; Abraham and Mathew, 2019 ) in response to the strong pressure manipulation (right hand), result in a distinct tactile representation in left S1 during CS− trials (pressure task). This representation would be distinct from the representation of scanner-generic sensation (right hand) experienced during the caress (which was applied to the left hand).…”

Section: Discussionmentioning

confidence: 99%

Decomposing Neural Representational Patterns of Discriminatory and Hedonic Information during Somatosensory Stimulation

Kryklywy

Ehlers

Beukers

et al. 2022

eNeuro

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The ability to interrogate specific representations in the brain, determining how, and where, difference sources of information are instantiated can provide invaluable insight into neural functioning. Pattern component modelling (PCM) is a recent analytic technique for human neuroimaging that allows the decomposition of representational patterns in brain into contributing sub components. In the current study, we present a novel PCM variant that tracks the contribution of pre-specified representational patterns to brain representation across areas, thus allowing hypothesis-guided employment of the technique. We apply this technique to investigate the contributions of hedonic and non-hedonic information to the neural representation of tactile experience. We applied aversive pressure and appetitive brush to stimulate distinct peripheral nerve pathways for tactile information (C-/CT-fibers respectively) while patients underwent fMRI scanning. We performed representational similarity analyses with pattern component modeling to dissociate how discriminatory vs. hedonic tactile information contributes to population code representations in the human brain. Results demonstrated that information about appetitive and aversive tactile sensation is represented separately from non-hedonic tactile information across cortical structures. This also demonstrates the potential of new hypothesis-guided PCM variants to help delineate how information is instantiated in the brain.Synthesis StatementThis work provides a novel brain imaging analyses that enables the decomposition of brain states into subcomponent states each associated with distinct patterns of experience or information. This technique is applied to human neuroimaging data acquired during hedonic touch to demonstrate a dual role of somatosensation in affective and sensory experience.The analytic advancement highlights exciting new developments in human neuroscience, allowing for the decomposition of human experience into discrete representation state both within and across brain areas.

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“…Melanocytes are found in the basal layer and are responsible for the production of melanin, a skin pigment that absorbs UV-radiation and that determines the skin color [ 24 ]. Merkel cells are located in or near the basal layer and act as sensory receptors in the skin [ 25 ]. Langerhans cells are antigen presenting immune cells of the epidermis that are most prominent in the stratum spinosum.…”

Section: Skin Structurementioning

confidence: 99%

Modelling the Complexity of Human Skin In Vitro

et al. 2023

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The skin serves as an important barrier protecting the body from physical, chemical and pathogenic hazards as well as regulating the bi-directional transport of water, ions and nutrients. In order to improve the knowledge on skin structure and function as well as on skin diseases, animal experiments are often employed, but anatomical as well as physiological interspecies differences may result in poor translatability of animal-based data to the clinical situation. In vitro models, such as human reconstructed epidermis or full skin equivalents, are valuable alternatives to animal experiments. Enormous advances have been achieved in establishing skin models of increasing complexity in the past. In this review, human skin structures are described as well as the fast evolving technologies developed to reconstruct the complexity of human skin structures in vitro.

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Merkel cells: A collective review of current concepts

Cited by 40 publications

References 59 publications

A peripheral CB2 cannabinoid receptor mechanism suppresses chemotherapy-induced peripheral neuropathy: evidence from a CB2 reporter mouse

A peripheral CB2 cannabinoid receptor mechanism suppresses chemotherapy-induced peripheral neuropathy: evidence from a CB2 reporter mouse

Decomposing Neural Representational Patterns of Discriminatory and Hedonic Information during Somatosensory Stimulation

Modelling the Complexity of Human Skin In Vitro

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