A Pharmacological Interactome Platform for Discovery of Pain Mechanisms and Targets

Wangzhou, Andi; Paige, Candler; Neerukonda, Sanjay V.; Dussor, Gregory; Ray, Pradipta; Price, Theodore J.

doi:10.2139/ssrn.3600957

Cited by 4 publications

(6 citation statements)

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“…Glial factors may also influence the expression and/or function of nociceptive channels such as transient receptor potential ankyrin 1, vanilloid 1 and 4 (TRPA1, TRPV1, TRPV4), purinergic P2X 3 receptors, tetrodotoxin-insensitive sodium channels Na v 1.8 and Na v 1.9, and T-type calcium channels Ca v 3.2 ( Beyak et al, 2004 ; Brierley et al, 2008 , 2009 ; Brierley and Linden, 2014 ; Cenac et al, 2010 ; De Schepper et al, 2008 ; Hockley et al, 2014 ; Lapointe et al, 2015 ; Scanzi et al, 2016 ; Wynn et al, 2004 ). Additionally, growth factors such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glia-derived neurotrophic factor (GDNF) are secreted by glia in response to proinflammatory cytokines ( Delvalle et al, 2018 ; von Boyen et al, 2006 ) and could modify nociceptor sensitivity ( Dubin et al, 2012 ; Prato et al, 2017 ; Wangzhou et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Enteric Glia Modulate Macrophage Phenotype and Visceral Sensitivity following Inflammation

et al. 2020

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SUMMARY Mechanisms resulting in abdominal pain include altered neuro-immune interactions in the gastrointestinal tract, but the signaling processes that link immune activation with visceral hypersensitivity are unresolved. We hypothesized that enteric glia link the neural and immune systems of the gut and that communication between enteric glia and immune cells modulates the development of visceral hypersensitivity. To this end, we manipulated a major mechanism of glial intercellular communication that requires connexin-43 and assessed the effects on acute and chronic inflammation, visceral hypersensitivity, and immune responses. Deleting connexin-43 in glia protected against the development of visceral hypersensitivity following chronic colitis. Mechanistically, the protective effects of glial manipulation were mediated by disrupting the glial-mediated activation of macrophages through the macrophage colony-stimulating factor. Collectively, our data identified enteric glia as a critical link between gastrointestinal neural and immune systems that could be harnessed by therapies to ameliorate abdominal pain.

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Section: Discussionmentioning

confidence: 99%

Enteric Glia Modulate Macrophage Phenotype and Visceral Sensitivity following Inflammation

et al. 2020

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“…The DGIdb database was used to identify known drugs (Cotto et al, 2018) that target proteins in our identified interactomes. The interactome database is described in detail in our previous work (Wangzhou et al, 2020).…”

Section: Data Sourcesmentioning

confidence: 99%

“…Based on a database (Szklarczyk et al, 2019) and the literature, corresponding receptors or ligands for these additional genes were identified and added to the list of ligand-receptor pairs. A total of 3098 pairs of ligand-receptor interactions were used in the interactome analysis for all possible ligand-receptor interactions (Wangzhou et al, 2020).…”

Section: Creation Of a Ligand Receptor Signaling Interactome Databasementioning

confidence: 99%

“…In these cases, the gene for the upstream signaling molecule was analyzed in lieu of the ligand, and the gene for the downstream signaling molecule in lieu of the receptor. The entire interactome database is described in detail in (Wangzhou et al, 2020).…”

Section: Creation Of a Ligand Receptor Signaling Interactome Databasementioning

confidence: 99%

“…Using an interactome-based framework we have described previously (Wangzhou et al, 2020) to find high-value pharmacologically relevant targets, we identify new, potential intervention points to reduce disease burden in patients with existing or under-development drugs. A key finding emerging from the data is that certain interventions used or under development for rheumatic or neuropathic pain might be useful against COVID-19.…”

Section: Introductionmentioning

confidence: 99%

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Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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A Pharmacological Interactome Platform for Discovery of Pain Mechanisms and Targets

Cited by 4 publications

References 0 publications

Enteric Glia Modulate Macrophage Phenotype and Visceral Sensitivity following Inflammation

Enteric Glia Modulate Macrophage Phenotype and Visceral Sensitivity following Inflammation

A pharmacological interactome between COVID-19 patient samples and human sensory neurons reveals potential drivers of neurogenic pulmonary dysfunction

Research on Pain Information Management System Based on Deep Learning

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