Peripheral Neuronal Mechanism of Itch: Histamine and Itch

Histamine,; Thurmond, Itch Robin L.; Kazerouni, Kayvan; Chaplan, Sandra R.; Greenspan, Andrew

doi:10.1201/b16573-14

Cited by 14 publications

(10 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The three male donor DRG pairs with pain in one dermatome, but not the other, were each analysed for differentially-expressed genes (Table 2 and Supplementary Tables 3 and 4). Several signalling pathways were enriched in the gene set upregulated in pain samples, including the TNF-alpha, TGF-beta, MAPK and TLR pathways (Letterio and Roberts, 1998;Morikawa et al, 2004;Wei et al, 2013;Cevikbas et al, 2014). Transcription factors linked to neuropathic pain in preclinical models, including FOS, FOSB and ATF3, and a number of well-known cytokine ligands including TNF, IL6 and CCL3 were also upregulated in at least two of the three pairs.…”

Section: Resultsmentioning

confidence: 97%

Electrophysiological and transcriptomic correlates of neuropathic pain in human dorsal root ganglion neurons

North

Ray

et al. 2019

Brain

231

217

View full text Add to dashboard Cite

Neuropathic pain encompasses a diverse array of clinical entities affecting 7–10% of the population, which is challenging to adequately treat. Several promising therapeutics derived from molecular discoveries in animal models of neuropathic pain have failed to translate following unsuccessful clinical trials suggesting the possibility of important cellular-level and molecular differences between animals and humans. Establishing the extent of potential differences between laboratory animals and humans, through direct study of human tissues and/or cells, is likely important in facilitating translation of preclinical discoveries to meaningful treatments. Patch-clamp electrophysiology and RNA-sequencing was performed on dorsal root ganglia taken from patients with variable presence of radicular/neuropathic pain. Findings establish that spontaneous action potential generation in dorsal root ganglion neurons is associated with radicular/neuropathic pain and radiographic nerve root compression. Transcriptome analysis suggests presence of sex-specific differences and reveals gene modules and signalling pathways in immune response and neuronal plasticity related to radicular/neuropathic pain that may suggest therapeutic avenues and that has the potential to predict neuropathic pain in future cohorts.

show abstract

Section: Resultsmentioning

confidence: 97%

Electrophysiological and transcriptomic correlates of neuropathic pain in human dorsal root ganglion neurons

North

Ray

et al. 2019

Brain

231

217

View full text Add to dashboard Cite

show abstract

“…121 Until recently, T cells were thought to be a major source of IL-31. 121,101 However, Niyonsaba et al, 122 found that MCs express IL-31 and its expression is elevated in psoriatic human skin MCs. In addition, keratinocyte-derived HDPs such as hBDs induce the expression and release of IL-31 from human MCs.…”

Section: Potential Roles Of Mrgprx2 On Neurogenic Inflammation Pain mentioning

confidence: 99%

Roles of Mas-related G protein–coupled receptor X2 on mast cell–mediated host defense, pseudoallergic drug reactions, and chronic inflammatory diseases

Subramanian¹,

Gupta

Ali

2016

Journal of Allergy and Clinical Immunology

325

312

View full text Add to dashboard Cite

Mast cells (MCs), which are granulated tissue-resident cells of hematopoietic lineage, contribute to vascular homeostasis, innate/adaptive immunity and wound healing. MCs are, however, best known for their roles in allergic and inflammatory diseases such as anaphylaxis, food allergy, rhinitis, itch, urticaria, atopic dermatitis and asthma. In addition to the high affinity IgE receptor (FcεRI), MCs express numerous G protein coupled receptors (GPCRs), which are the largest group of membrane receptor proteins and are the most common targets of drug therapy. Antimicrobial host defense peptides (HDPs), neuropeptides (NPs), major basic protein (MBP), eosinophil peroxidase (EPO) and many FDA approved peptidergic drugs activate human MCs via a novel GPCR known as MAS-related G protein coupled receptor-X2 (MRGPRX2; formerly known as MrgX2). Unique features of MRGPRX2 that distinguish it from other GPCRs include their presence both on plasma membrane and intracellular sites and their selective expression in MCs. In this article, we review the possible roles of MRGPRX2 on host defense, drug-induced anaphylactoid reactions, neurogenic inflammation, pain, itch and chronic inflammatory diseases such as urticaria and asthma. We propose that HDPs that kill microbes directly and activate MCs via MRGPRX2 could serve as novel GPCR targets to modulate host defense against microbial infection. Furthermore, monoclonal antibodies or small molecule inhibitors of MRGPRX2 could be developed for the treatment of MC-dependent allergic and inflammatory disorders.

show abstract

“…Cytokines can act on a number of different targets including immune cells, keratinocytes, and even sensory nerves (Fig. 2) (32). Some of the newer cytokines used as targets in regard to treating itch are discussed below and include IL4, IL13, IL31, and IL17.…”

Section: Interleukin Antagonistsmentioning

confidence: 99%

A New Generation of Treatments for Itch

Fowler¹,

Yosipovitch²

2020

Acta Derm Venerol

View full text Add to dashboard Cite

Itch is a pesky sensation that can be difficult to eliminate. Although a mainstay of anti-itch therapy for many decades, antihistamines are not an effective therapy for patients with chronic, unrelenting itch. With a greater understanding of itch, newer treatments have been developed that are much more effective. These include drugs targeting the neural system and drugs that affect the immune system. For decades, antihistamines have been the mainstay of treatment for chronic pruritus, yet they often only work by making patients drowsy and forgetful of their itch. A new era of antipruritic drugs is quickly approaching, presenting more effective treatments for patients suffering from chronic itch. Several treatments have been developed targeting specific receptors in the nervous system, such as the transient receptor potential channels, sodium channels, neurokinin-1 receptors, opioid receptors, and many more. Additionally, antipruritic therapies developed to work on the immune system have become more targeted, leading to greater safety and efficacy measures. These include crisaborole, several interleukin antagonists, and janus kinase inhibitors. The promising results presented with these new antipruritic therapies allow physicians to be better equipped to treat their itchy patients.

show abstract

Peripheral Neuronal Mechanism of Itch: Histamine and Itch

Cited by 14 publications

References 1 publication

Electrophysiological and transcriptomic correlates of neuropathic pain in human dorsal root ganglion neurons

Electrophysiological and transcriptomic correlates of neuropathic pain in human dorsal root ganglion neurons

Roles of Mas-related G protein–coupled receptor X2 on mast cell–mediated host defense, pseudoallergic drug reactions, and chronic inflammatory diseases

A New Generation of Treatments for Itch

Contact Info

Product

Resources

About