Role of Mast Cells in the Pathogenesis of Pruritus in Mastocytosis

Acta Dermato Venereologica ◽

10.2340/actadv.v101.350 ◽

2021 ◽

Author(s):

Dominika Kwiatkowska ◽

Adam Reich

Keyword(s):

Mast Cells ◽

Neurogenic Inflammation ◽

Treatment Options ◽

Sensory Nerve ◽

Neurokinin A ◽

Calcitonin Gene ◽

Abnormal Accumulation ◽

Mutual Communication

Pruritus can be defined as an unpleasant sensation that evokes a desire to scratch and significantly impairs patients’ quality of life. Pruritus is widely observed in many dermatoses, including mastocytosis, a rare disease characterized by abnormal accumulation of mast cells, which can involve skin, bone marrow, and other organs. Increasing evidence highlights the role of mast cells in neurogenic inflammation and itching. Mast cells release various pruritogenic mediators, initiating subsequent mutual communication with specific nociceptors on sensory nerve fibres. Among important mediators released by mast cells that induce pruritus, one can distinguish histamine, serotonin, proteases, as well as various cytokines. During neuronal-induced inflammation, mast cells may respond to numerous mediators, including neuropeptides, such as substance P, neurokinin A, calcitonin gene-related peptide, endothelin 1, and nerve growth factor. Currently, treatment of pruritus in mastocytosis is focused on alleviating the effects of mediators secreted by mast cells. However, a deeper understanding of the intricacies of the neurobiology of this disease could help to provide better treatment options for patients.

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Relationships between permeable vessels, nerves, and mast cells in rat cutaneous neurogenic inflammation

Journal of Applied Physiology ◽

10.1152/jappl.1990.68.6.2305 ◽

1990 ◽

Vol 68 (6) ◽

pp. 2305-2311 ◽

Cited By ~ 42

Author(s):

J. N. Baraniuk ◽

M. L. Kowalski ◽

M. A. Kaliner

Keyword(s):

Electrical Stimulation ◽

Mast Cells ◽

Neurogenic Inflammation ◽

Sensory Nerve ◽

Nerve Fibers ◽

Sensory Nerves ◽

Neurokinin A ◽

Rat Skin ◽

Protein Extravasation ◽

Stimulation Of

Electrical stimulation of rat sensory nerves produces cutaneous vasodilation and plasma protein extravasation, a phenomenon termed “neurogenic inflammation”. Rat skin on the dorsum of the paw developed neurogenic inflammation after electrical stimulation of the saphenous nerve. In tissue sections, the extravasation of the supravital dye monastral blue B identified permeable vessels. Mast cells were identified by toluidine blue stain. Permeable vessels were significantly more dense in the superficial 120 microns of the dermis than in the deeper dermis, whereas mast cells were significantly more frequent in the deeper dermis. The relationships between nociceptive sensory nerve fibers, permeable vessels, and mast cells were examined by indirect immunohistochemistry for calcitonin gene-related peptide (CGRP), neurokinin A (NKA), and substance P (SP). CGRP-, NKA-, and SP-containing nerves densely innervated the superficial dermis and appeared to innervate the vessels that became permeable during neurogenic inflammation. In contrast, mast cells were not associated with either permeable vessels or nerve fibers. These data suggest that electrical stimulation of rat sensory nerves produces vascular permeability by inducing the release of neuropeptides that may directly stimulate the superficial vascular bed. Mast cells may not be involved in this stage of cutaneous neurogenic inflammation in rat skin.

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Thrombopoietin Receptor Agonists in Children with Immune Thrombocytopenia: A New Therapeutic Era

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200531142244 ◽

2020 ◽

Vol 20 ◽

Author(s):

Giuseppe Lassandro ◽

Valentina Palladino ◽

Giovanni Carlo Del Vecchioa ◽

Viviana Valeria Palmieri ◽

Paola Carmela Corallo ◽

...

Keyword(s):

Immune Thrombocytopenia ◽

Treatment Options ◽

Thrombopoietin Receptor Agonists ◽

Receptor Agonists ◽

Thrombopoietin Receptor ◽

Related Quality ◽

Health Related

Background and Objective: Immune thrombocytopenia (ITP) is a common bleeding disorder in childhood. The management of ITP in children is controversial, requiring personalized assessment of patients and therapeutic choices. Thrombopoietin receptor agonists (TPO-RAs), eltrombopag and romiplostim, have been shown to be safety and effective for the treatment of pediatric ITP. The aim of our research is defining the role of thrombopoietin receptor agonists in the management of pediatric ITP. Method: This review focuses on the use of TPO-RAs in pediatric ITP, in randomized trials and in clinical routine, highlighting their key role in management of the disease. Results: Eltrombopag and romiplostim appear effective treatment options for children with ITP. Several clinical studies have assessed that the use of TPO-RAs increases platelet count, decreases bleeding symptoms and improves health-related quality of life. Moreover, TPO-RAs are well tolerated with minor side effects. Conclusion: Although TPO-RAs long term efficacy and safety still require further investigations, their use is gradually expanding in clinical practice of children with ITP.

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Interactions between Chemesthesis and Taste: Role of TRPA1 and TRPV1

International Journal of Molecular Sciences ◽

10.3390/ijms22073360 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3360

Author(s):

Mee-Ra Rhyu ◽

Yiseul Kim ◽

Vijay Lyall

Keyword(s):

Transient Receptor Potential ◽

Taste Receptor ◽

Sensory Nerve ◽

Receptor Potential ◽

Transient Receptor Potential Vanilloid ◽

Trpv1 Channels ◽

Trigeminal Neurons ◽

Calcitonin Gene ◽

Transient Receptor

In addition to the sense of taste and olfaction, chemesthesis, the sensation of irritation, pungency, cooling, warmth, or burning elicited by spices and herbs, plays a central role in food consumption. Many plant-derived molecules demonstrate their chemesthetic properties via the opening of transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) channels. TRPA1 and TRPV1 are structurally related thermosensitive cation channels and are often co-expressed in sensory nerve endings. TRPA1 and TRPV1 can also indirectly influence some, but not all, primary taste qualities via the release of substance P and calcitonin gene-related peptide (CGRP) from trigeminal neurons and their subsequent effects on CGRP receptor expressed in Type III taste receptor cells. Here, we will review the effect of some chemesthetic agonists of TRPA1 and TRPV1 and their influence on bitter, sour, and salt taste qualities.

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Release of Histamine from Dural Mast Cells by Substance P and Calcitonin Gene-Related Peptide

Cephalalgia ◽

10.1046/j.1468-2982.1997.1703166.x ◽

1997 ◽

Vol 17 (3) ◽

pp. 166-174 ◽

Cited By ~ 133

Author(s):

A Ottosson ◽

L Edvinsson

Keyword(s):

Mast Cells ◽

Substance P ◽

Histamine Release ◽

Dura Mater ◽

Neurogenic Inflammation ◽

Calcitonin Gene Related Peptide ◽

Sampling Procedure ◽

Related Peptide ◽

Calcitonin Gene ◽

Peritoneal Mast Cells

The aim of the present study was to examine if the neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) can stimulate histamine release from mast cells in the dura mater and thereby play a role in cranial vasoregulation and local neurogenic inflammation. Dura mater mast cells were compared with peritoneal mast cells in the rat. Histamine was released from dura mater mast cells by compound 48/80, SP and CGRP but from peritoneal mast cells only by compound 8/80 and SP. NPY and VIP released quite small amounts of histamine from dural mast cells. The release on SP and CGRP from rat dura mater mast cells was blocked by the receptor antagonists FK888 and CGRP8-37 respectively, suggesting receptor mediated release mechanisms. None of the stimuli released histamine from human or porcine dural mast cells, possibly because the sampling procedure injures and incapacitates the cells.

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Pharmacotherapy review: Emerging treatment modalities in transthyretin cardiac amyloidosis

American Journal of Health-System Pharmacy ◽

10.1093/ajhp/zxab356 ◽

2021 ◽

Author(s):

Emily Plumadore ◽

Lindsay Lombardo ◽

Katherine P Cabral

Keyword(s):

Treatment Options ◽

Disease State ◽

Treatment Modalities ◽

Limited Data ◽

Limited Evidence ◽

Agent Selection ◽

Selection For ◽

Tea Extract

Abstract Disclaimer In an effort to expedite the publication of articles , AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose This review aims to summarize the evidence and pharmacological characteristics of treatment options for transthyretin amyloid cardiomyopathy (ATTR-CM). Additionally, this review highlights the role of clinical pharmacists in helping to secure newly introduced therapies. Summary ATTR-CM, a disease characterized by misfolded protein that is deposited in the myocardium and disrupts cardiac functioning, has historically been underdiagnosed due to the need for invasive biopsy and an illusion of rarity. Once diagnosed, limited treatment modalities for ATTR-CM have led providers to rely on nonpharmacological remedies or off-label use of medications with limited evidence of benefit. However, recent noninvasive diagnostic advancements and heightened disease state awareness have revealed increased prevalence of ATTR-CM. This has led to the introduction of several first-in-class pharmaceuticals with actions targeted at inhibiting the various phases of amyloidosis: TTR stabilizers include diflunisal and first-in-class, Food and Drug Administration (FDA)-approved tafamidis; TTR silencers include patisiran and inotersen; fibril disrupters include doxycycline with tauroursodeoxycholic acid; and alternative agents include green tea extract and curcumin. Conclusion ATTR-CM treatments have emerged and, despite current limited data, are continuing to evolve. Tafamidis, the only agent approved by FDA for ATTR-CM, shows promise to improve survival and quality of life in patients with ATTR-CM. Pharmacists can play a key role in assisting with agent selection for this disease state, as well as providing knowledge about current and future clinical trials evaluating the safety and efficacy of the available treatment modalities.

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The role of erenumab in the treatment of migraine

Therapeutic Advances in Neurological Disorders ◽

10.1177/1756286420927119 ◽

2020 ◽

Vol 13 ◽

pp. 175628642092711 ◽

Cited By ~ 1

Author(s):

Anna P. Andreou ◽

Matteo Fuccaro ◽

Giorgio Lambru

Keyword(s):

Clinical Trials ◽

Side Effects ◽

European Medicines Agency ◽

Human Antibody ◽

Subcutaneous Injections ◽

Calcitonin Gene ◽

The Us ◽

Different Doses

Calcitonin gene related peptide (CGRP) monoclonal antibodies (mAbs) have been the first class of specifically developed preventive treatments for migraine. Clinical trials data suggest superiority of the CGRP mAbs to placebo in terms of prevention of migraine symptoms, migraine-specific quality of life and headache related disability. Treatment-related side effects overall did not differ significantly from placebo and discontinuation rate due to side effects has been low across the clinical trials, perhaps in view of their peripheral mode of action. Along with their route and frequency of administration, these novel class of drugs may constitute an improvement compared with the established arsenal of migraine treatments. Erenumab is a fully human antibody and the only mAb acting on the CGRP pathway by blocking its receptor. It is the first of the CGRP mAb class approved by the US Food and Drug Administration (May 2018) and the European Medicines Agency (July 2018). Erenumab exists in two different doses (70 mg and 140 mg) and it is administered with monthly subcutaneous injections. This review summarises erenumab pharmacological characteristics, clinical trials data, focusing on the potential role of this treatment in clinical practice.

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Neurogenic Control of Cerebral Circulation

Cephalalgia ◽

10.1177/03331024850050s205 ◽

1985 ◽

Vol 5 (2_suppl) ◽

pp. 25-33 ◽

Cited By ~ 27

Author(s):

G Burnstock

Keyword(s):

Substance P ◽

Sensory Nerve ◽

Sympathetic Nerves ◽

Purine Nucleotides ◽

Axon Reflex ◽

Calcitonin Gene ◽

Perivascular Nerves ◽

Neuromuscular Apparatus ◽

Perivascular Nerve Plexus

The cerebral vascular neuromuscular apparatus consists of a varicose perivascular nerve plexus at the adventitial-medial border and smooth muscle cells in the medial coat that are functionally connected. In addition to noradrenaline and acetylcholine, a number of putative non-adrenergic, non-cholingergic neurotransmitters have been identified in cerebral perivascular nerves, including serotonin, substance P, vasoactive intestinal polypeptide, gastrinreleasing peptide, cholecystokinin, somatostatin, neurotensin, calcitonin gene-related peptide and neuropeptide Y. The role of adenosine-5'-triphosphate as a cotransmitter with noradrenaline in some perivascular sympathetic nerves, and of endothelial cells in mediating the vasodilatation produced by some neurohumoral agents is discussed. Speculations are made about the relation between vascular neuroeffector mechanisms and migraine, including the possiblity of local vasospasm by serotoninergic nerves, reactive hyperaemia involving purine nucleotides and nucleosides, release of substance P from sensory nerve collaterals during antidromic ('axon reflex') impulses and secondary release of local agents such as prostanoids, histamine and bradykinin.

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Calcitonin gene-related peptide, neurokinin A and substance P: Effects on Nociception and neurogenic inflammation in human skin and temporal muscle

Peptides ◽

10.1016/0196-9781(91)90022-h ◽

1991 ◽

Vol 12 (2) ◽

pp. 333-337 ◽

Cited By ~ 96

Author(s):

Ulrik Pedersen-Bjergaard ◽

Lars Bøgeskov Nielsen ◽

Kai Jensen ◽

Lars Edvinsson ◽

Inger Jansen ◽

...

Keyword(s):

Substance P ◽

Human Skin ◽

Neurogenic Inflammation ◽

Calcitonin Gene Related Peptide ◽

Neurokinin A ◽

Temporal Muscle ◽

Related Peptide ◽

Calcitonin Gene

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Pressure ulcers: Current understanding and newer modalities of treatment

Indian Journal of Plastic Surgery ◽

10.4103/0970-0358.155260 ◽

2015 ◽

Vol 48 (01) ◽

pp. 004-016 ◽

Cited By ~ 49

Author(s):

Surajit Bhattacharya ◽

R. K. Mishra

Keyword(s):

Pressure Ulcers ◽

Treatment Options ◽

Healing Process ◽

Treatment Algorithm ◽

Wound Debridement ◽

Advantages And Disadvantages ◽

Prone Area ◽

Long Time

ABSTRACTThis article reviews the mechanism, symptoms, causes, severity, diagnosis, prevention and present recommendations for surgical as well as non-surgical management of pressure ulcers. Particular focus has been placed on the current understandings and the newer modalities for the treatment of pressure ulcers. The paper also covers the role of nutrition and pressure-release devices such as cushions and mattresses as a part of the treatment algorithm for preventing and quick healing process of these wounds. Pressure ulcers develop primarily from pressure and shear; are progressive in nature and most frequently found in bedridden, chair bound or immobile people. They often develop in people who have been hospitalised for a long time generally for a different problem and increase the overall time as well as cost of hospitalisation that have detrimental effects on patient’s quality of life. Loss of sensation compounds the problem manifold, and failure of reactive hyperaemia cycle of the pressure prone area remains the most important aetiopathology. Pressure ulcers are largely preventable in nature, and their management depends on their severity. The available literature about severity of pressure ulcers, their classification and medical care protocols have been described in this paper. The present treatment options include various approaches of cleaning the wound, debridement, optimised dressings, role of antibiotics and reconstructive surgery. The newer treatment options such as negative pressure wound therapy, hyperbaric oxygen therapy, cell therapy have been discussed, and the advantages and disadvantages of current and newer methods have also been described.

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