Methods for Preclinical Assessment of Antipruritic Agents and Itch Mechanisms Independent of Mast-Cell Histamine

Kuraishi, Yasushi

doi:10.1248/bpb.b15-00090

Cited by 14 publications

(12 citation statements)

References 116 publications

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“…Systemic diseases. Dry skin is also a common cutaneous manifestation in pruritic internal diseases, such as CKD, CLD, and DM (4). Skin dryness may appear at different stages of CKD, but it is more frequently diagnosed in dialysis subjects (45%) (15).…”

Section: Dry Skinmentioning

confidence: 99%

Mechanisms and Management of Itch in Dry Skin

Moniaga¹,

Tominaga²,

Takamori³

2020

Acta Derm Venerol

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Itch is an unpleasant sensation that may disturb quality of life, and for which the pathomechanism and appropriate treatments are unclear. Chronic itch, which lasts more than 6 weeks, often accompanies pathological dry skin-based conditions, such as xerosis, atopic dermatitis, liver and kidney diseases. A decline in skin barrier function is thought to be the primary cause of itch induced by dry skin. Many kinds of mediators, receptors, and channels are involved in itch signalling among the skin nervous system, skin cells, and central nervous system. Several therapeutic options for itching have thus been developed, such as phototherapy, phospholipids, antioxidants, and emollients. Chronic itch is a burdensome clinical problem that often accompanies pathological dry skin-based conditions, such as atopic dermatitis, and systemic disorders, such as kidney diseases, with an unclear pathomechanism and treatments. One of the basic mouse models to investigate mechanisms of itch associated with dry skin is a mixture of acetone and ether followed by water. Animal studies using the acetone and ether followed by water model have revealed that many mediators and receptors, e.g. mas-related G protein-coupled receptor family, transient receptor potential, and chemokines, are responsible for itch and its hypersensitivity, supporting the hypothesis that dry skin-induced itch is a histamine-independent pathway. New insights have been acquired into the interplay between neurones and non-neuronal cells in the initiation, modulation, and sensitization of itch. Several thera peutic options for itching have thus been developed. This review summarizes the updated pathogenesis and therapeutic strategies for itch in dry skin conditions.

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Section: Dry Skinmentioning

confidence: 99%

Mechanisms and Management of Itch in Dry Skin

Moniaga¹,

Tominaga²,

Takamori³

2020

Acta Derm Venerol

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“…Advances in understanding the mechanisms of acute and chronic itch have been achieved by the development of animal models. For chronic itch, several models have been established, most of which focus on cutaneous skin diseases, including atopic dermatitis, contact dermatitis and xerosis (dry skin) [84][85][86]. Recently, several studies have uncovered that glial cells in the SDH are crucial for itch chronicity.…”

Section: Chronic Itch and Sdh Astrocytesmentioning

confidence: 99%

Modulation of Pain and Itch by Spinal Glia

Tsuda

2017

Neurosci. Bull.

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Chronic pain and itch are a pathological operation of the somatosensory system at the levels of primary sensory neurons, spinal cord and brain. Pain and itch are clearly distinct sensations, and recent studies have revealed the separate neuronal pathways that are involved in each sensation. However, the mechanisms by which these sensations turn into a pathological chronic state are poorly understood. A proposed mechanism underlying chronic pain and itch involves abnormal excitability in dorsal horn neurons in the spinal cord. Furthermore, an increasing body of evidence from models of chronic pain and itch has indicated that synaptic hyperexcitability in the spinal dorsal horn might not be a consequence simply of changes in neurons, but rather of multiple alterations in glial cells. Thus, understanding the key roles of glial cells may provide us with exciting insights into the mechanisms of chronicity of pain and itch, and lead to new targets for treating chronic pain and itch.

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“…In the skin, MCs are also associated with itch sensations elicited by immunologic and non-immunologic stimulation. 4 , 5 …”

Section: Introductionmentioning

confidence: 99%

Apoptotic resistance of human skin mast cells is mediated by Mcl-1

et al. 2017

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Mast cells (MCs) are major effector cells of allergic reactions and contribute to multiple other pathophysiological processes. MCs are long-lived in the tissue microenvironment, in which they matured, but it remains ill-defined how longevity is established by the natural habitat, as research on human MCs chiefly employs cells generated and expanded in culture. In this study, we report that naturally differentiated skin MCs exhibit substantial resilience to cell death with considerable portions surviving up to 3 days in the complete absence of growth factors (GF). This was evidenced by kinetic resolution of membrane alterations (Annexin-V, YoPro), DNA degradation (propidium iodide), mitochondrial membrane disruption (Depsipher), and Caspase-3 activity. Because of the high basal survival, further protection by SCF was modest. Conversely, survival was severely compromised by staurosporine, implying functional caspase machinery. Contrary to the resistance of freshly purified MCs, their culture-expanded counterpart readily underwent cell death upon GF deprivation. Searching for the molecular underpinnings explaining the difference, we identified Mcl-1 as a critical protector. In fact, silencing Mcl-1 by RNAi led to impaired survival in skin MCs ex vivo, but not their cultured equivalent. Therefore, MCs matured in the skin have not only higher expression of Mcl-1 than proliferating MCs, but also greater reliance on Mcl-1 for their survival. Collectively, we report that human skin MCs display low susceptibility to cell death through vast expression of Mcl-1, which protects from mortality and may contribute to MC longevity in the tissue.

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Methods for Preclinical Assessment of Antipruritic Agents and Itch Mechanisms Independent of Mast-Cell Histamine

Cited by 14 publications

References 116 publications

Mechanisms and Management of Itch in Dry Skin

Mechanisms and Management of Itch in Dry Skin

Modulation of Pain and Itch by Spinal Glia

Apoptotic resistance of human skin mast cells is mediated by Mcl-1

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