Crosstalk between Mu-Opioid receptors and neuroinflammation: Consequences for drug addiction and pain

Neuroscience & Biobehavioral Reviews, Journal Year: 2022, Volume and Issue: 145, P. 105011 - 105011

Published: Dec. 21, 2022

A C T Mu-Opioid Receptors (MORs) are well-known for participating in analgesia, sedation, drug addiction, and other physiological functions.Although MORs have been related to neuroinflammation their biological mechanism remains unclear.It is suggested that work alongside Toll-Like enhance the release of proinflammatory mediators cytokines during pathological conditions.Some cytokines, including TNF-α, IL-1β IL-6, postulated regulate levels by both avoiding MOR recycling enhancing its production.In addition, Neurokinin-1 Receptor, also affected neuroinflammation, could be regulating trafficking.Therefore, inflammation central nervous system seems associated with altered/ increased expression, which might harmful processes, such as addiction pain.Here, we provide a critical evaluation on MORs' role implication these conditions.Understanding functioning, regulation implications pain may help elucidate potential therapeutic use against conditions disorders. receptorsMu-Opioid belong family Opioid (ORs), metabotropic receptors binding opioidergic drugs morphine heroin.Other members ORs include Delta (DOR), Kappa (KOR) opioid receptor like-1 (ORL1).All can bind differential affinity distinct endogenous (own produced organisms) opioids, endorphins (recognized MORs), enkephalins (DORs), dynorphins (KORs) nociceptins (ORL1) (Bodnar, 2022).ORs differ distribution within system.MORs, DORs ORL1 widespread (CNS), whereas KORs more restricted midline ventral structures (Allen Institute Brain Science, 2011).ORs participate many processes neuroprotection, respiratory control, ionic homeostasis, peristalsis, mood regulation, cardioprotection among others (reviewed elsewhere: Shenoy Lui, 2018).The effects opioids depend where they receptors, cell type on, specific receptor(s) bind.In particular, produce euphoria, reinforcement, dysphoria, miosis, truncal rigidity, hedonia, aversion, nausea, reduce rate respiration cough reflex CNS (McNicol et al., 2003;Hyman 2006;Le Merrer 2009;Al-Hasani Bruchas, 2011; Castro Berridge, 2014a).Interestingly, activation different result opposite outcomes.Indeed, mesocorticolimbic (MCLS) induces leads dysphoric

Language: Английский

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Neurogenic inflammation as a novel treatment target for chronic pain syndromes

Experimental Neurology, Journal Year: 2022, Volume and Issue: 356, P. 114108 - 114108

Published: May 10, 2022

Language: Английский

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Gut microbiota modulates visceral sensitivity through calcitonin gene-related peptide (CGRP) production

Gut Microbes, Journal Year: 2023, Volume and Issue: 15(1)

Published: March 20, 2023

Abdominal pain is common in patients with gastrointestinal disorders, but its pathophysiology unclear, part due to poor understanding of basic mechanisms underlying visceral sensitivity. Accumulating evidence suggests that gut microbiota an important determinant Clinical and research studies also show sex plays a role perception, although the precise pathways are not elucidated. We investigated responses germ-free conventionally raised mice both sexes, assessed sensitivity colorectal distension, neuronal excitability dorsal root ganglia (DRG) neurons production substance P calcitonin gene-related peptide (CGRP) response capsaicin or mixture G-protein coupled receptor (GPCR) agonists. Germ-free displayed greater vivo colonic distention than conventional mice, no differences between males females. Pretreatment intracolonic GPCR agonists increased conventional, mice. In DRG neurons, had effect on activation by While stimulated was similar additional sex, CGRP higher mainly Absence increases male female This is, at least part, which evident However, central likely involved this process.

Language: Английский

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Neuropathic Corneal Pain: Tear Proteomic and Neuromediator Profiles, Imaging Features, and Clinical Manifestations

American Journal of Ophthalmology, Journal Year: 2024, Volume and Issue: 265, P. 6 - 20

Published: March 21, 2024

To investigate the tear proteomic and neuromediator profiles, in vivo confocal microscopy (IVCM) imaging features, clinical manifestations neuropathic corneal pain (NCP) patients.

Language: Английский

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Infrapatellar fat pad-derived MSC response to inflammation and fibrosis induces an immunomodulatory phenotype involving CD10-mediated Substance P degradation

Scientific Reports, Journal Year: 2019, Volume and Issue: 9(1)

Published: July 26, 2019

The infrapatellar fat pad (IFP) serves as a reservoir of Mesenchymal Stem Cells (MSC), and with adjacent synovium plays key roles in joint disease including the production Substance P (SP) affecting local inflammatory responses transmitting nociceptive signals. Here, we interrogate human IFP-derived MSC (IFP-MSC) reaction to pro-fibrotic environments (cell priming by TNFα/IFNγ TNFα/IFNγ/CTGF exposure respectively), compared bone marrow-derived (BM-MSC). Naïve IFP-MSC exhibit increased clonogenicity chondrogenic potential BM-MSC. Primed cells experienced dramatic phenotypic changes, sharp increase CD10, upregulation immunomodulatory transcripts, secreted growth factors/cytokines pathways (IL-10, TNF-α, MAPK, Ras PI3K-Akt). Naïve, more so primed (both) induced SP degradation vitro, reproduced their supernatants abrogated thiorphan, CD10 inhibitor. These findings were vivo rat model acute synovitis, where transiently engrafted reduction. Functionally, demonstrated sustained antagonism activated peripheral blood mononuclear (PBMC) proliferation, significantly outperforming declining dose-dependent effect naïve cohorts. Collectively, our vitro data supports cell way enhance immunoregulatory properties IFP-MSC, which selectively engraft areas active synovitis/IFP fibrosis inducing degradation, resulting cell-based product alternative BM-MSC potentially treat degenerative/inflammatory diseases.

Language: Английский

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