Mu‐opioid receptors in tachykinin‐1‐positive cells mediate the respiratory and antinociceptive effects of the opioid fentanyl DOI Creative Commons

Andreea Furdui,

Carolina da Silveira Scarpellini, Gaspard Montandon

et al.

British Journal of Pharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 6, 2024

Abstract Background and Purpose Opioid drugs are potent analgesics that carry the risk of respiratory side effects due to actions on μ ‐opioid receptors (MORs) in brainstem regions control respiration. Substance P is encoded by Tac1 gene expressed neurons regulating breathing, nociception, locomotion. Tac1‐ positive cells also express MORs mediating opioid‐induced depression. We determined role ‐positive opioid drugs. Experimental Approach In situ hybridization was used determine Oprm1 mRNA expression (gene encoding MORs) depression Conditional knockout mice lacking functional were produced locomotor responses analgesic fentanyl assessed using whole‐body plethysmography. A tail immersion assay assess antinociceptive response fentanyl. Key Results highly (>80%) subpopulations preBötzinger Complex, nucleus tractus solitarius, Kölliker–Fuse/lateral parabrachial region. Conditionally knocking out abolished rate, relative tidal volume, minute ventilation compared with mice. Importantly, eliminated cells, whereas induced preserved. Conclusions Implications Our findings suggest mediate depressive fentanyl, providing important insights for development pain therapies reduced effects.

Language: Английский

Muscles and Central Neural Networks Involved in Breathing: State of the Art DOI Open Access
Bruno Bordoni, Allan R Escher

Cureus, Journal Year: 2025, Volume and Issue: unknown

Published: March 15, 2025

Breathing is a systemic act, which involves not only the lungs, but entire body system. To have comprehensive clinical picture, it necessary to all patient's data; from this assumption, we can affirm that know muscles involved in breathing understand how obtain approach for care and treatment of patient improve respiratory capacity. The text reviews efferent connections centers cites are mechanism controlled managed by centers, starting muscular description cranial area, bucco-cervical cervicothoracic thoracic area. Knowing function accessory allows us obtain, some cases, valuable data prove predictive diagnostic path pathology. This first article literature, authors' knowledge, attempts list include single directly or indirectly breathing. goal narrative review remind clinicians researchers study different responses need analyze work skeletal musculature better what happens pathological physiological phases during step will allow individualize therapeutic training healthy subjects.

Language: Английский

Citations

1
Anatomical distribution of µ-opioid receptors, neurokinin-1 receptors, and vesicular glutamate transporter 2 in the mouse brainstem respiratory network DOI

Andreea Furdui,

Carolina da Silveira Scarpellini, Gaspard Montandon

et al.

Journal of Neurophysiology, Journal Year: 2024, Volume and Issue: 132(1), P. 108 - 129

Published: May 15, 2024

Opioid drugs can cause serious respiratory side-effects by binding to µ-opioid receptors (MORs) in brainstem regions that control breathing. To better understand the and their cellular subpopulations may be vulnerable modulation opioids, we provide a comprehensive map of Oprm1 (gene encoding MORs) mRNA expression throughout modulate Notably, identify glutamatergic neurokinin-1 receptor-expressing cells as potentially opioid worthy further investigation using targeted approaches.

Language: Английский

Citations

6
Effects of Fentanyl-Laced Cocaine on Circulating Ghrelin, Insulin, and Glucose Levels in Rats DOI Open Access

Huimei Wei,

Elise C. Maul,

Annet Kyomuhangi

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2341 - 2341

Published: March 6, 2025

Opioid mixed with cocaine has been increasingly implicated in overdose deaths, including both intentional co-use of opioid and fentanyl-adulterated drug supply. As ghrelin plays an important role reward can also influence insulin, this study aimed to assess responses the circulating ghrelin, glucose levels combined use fentanyl (a polydrug) rats by performing animal behavioral experiments biochemical analysis. The experimental data consistently revealed that significantly elevate acyl-ghrelin desacyl-ghrelin decrease insulin level without significant effects on level. These findings suggest that, like itself, fentanyl-cocaine polydrug self-promote its rewarding via elevating level, system might serve as a potential pharmacological target for treatment substance disorders caused polysubstance involving cocaine. Additionally, based obtained study, was always downregulated considerably, implying have stronger cardiovascular toxicity patients resistance diabetes. Further studies are required examine possibility.

Language: Английский

Citations

0
Characterizing the phenotype of pre-bötzinger complex neurons in rats DOI Creative Commons
Angela A. Connelly, Jaspreet K. Bassi,

Joshua J. Voger

et al.

Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0
A comparative examination of morphine and fentanyl: unravelling the differential impacts on breathing and airway stability DOI
Nicholas Burgraff, Nathan A. Baertsch, Jan‐Marino Ramirez

et al.

The Journal of Physiology, Journal Year: 2023, Volume and Issue: 601(20), P. 4625 - 4642

Published: Oct. 1, 2023

Abstract This study provides an in‐depth analysis of the distinct consequences opioid drugs morphine and fentanyl during opioid‐induced respiratory depression (OIRD). We explored physiological implications both on ventilation airway patency in anaesthetized mice. Our results revealed a similar reduction frequency with equivalent scaled dosages morphine, though onset suppression was more rapid fentanyl. Additionally, resulted transient airflow obstructions inspiratory cycle, which were absent following administration. Notably, these fentanyl‐specific eliminated tracheostomy, implicating upper airways as major factor contributing to fentanyl‐induced depression. further demonstrate that bronchodilators salbutamol adrenaline effectively reversed obstructions, highlighting bronchi's contribution obstruction. also uncovered significant sighs OIRD, by markedly reduced morphine. Finally, we found fentanyl‐exposed mice had survival under hypoxic conditions compared given demonstrating becomes lethal context hypoxaemia. findings shed light profound impacts opioids respiration stability lay foundation for improved use guidelines effective OIRD prevention strategies. image Key points Both significantly suppressed frequency, but faster Also, while increased tidal volume, this effect pronounced Fentanyl administration phase, suggesting its unique impact stability. obstruction not observed The administering such adrenaline. suggests possible therapeutic strategy mitigating adverse effects sighs, key mechanism prevent alveolar collapse. However, led complete cessation only their occurrence. Fentanyl‐treated showed ability survive those administered indicates hypoxaemia can vary based used.

Language: Английский

Citations

7
Effect of positive allosteric modulation and orthosteric agonism of dopamine D2-like receptors on respiration in mouse models of Rett syndrome DOI
Sebastian N. Maletz, Brandon T. Reid, David M. Baekey

et al.

Respiratory Physiology & Neurobiology, Journal Year: 2024, Volume and Issue: 328, P. 104314 - 104314

Published: Aug. 6, 2024

Language: Английский

Citations

1
Fentanyl Overdose Causes Prolonged Cardiopulmonary Dysregulation in Male SKH1 Mice DOI Creative Commons

Mackenzie Newman,

Heather Connery,

Swapna Kannan

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(7), P. 941 - 941

Published: July 14, 2024

Fentanyl overdose is a survivable condition that commonly resolves without chronic overt changes in phenotype. While the acute physiological effects of fentanyl overdose, such as opioid-induced respiratory depression (OIRD) and Wooden Chest Syndrome, represent immediate risks lethality, little known about longer-term systemic or organ-level impacts for survivors. In this study, we investigated single, bolus on components cardiopulmonary system up to one week post. SKH1 mice were administered subcutaneous at highest non-lethal dose (62 mg/kg), LD10 (110 LD50 (135 before euthanasia 40 min, 6 h, 24 7 d post-exposure. The cerebral cortex, heart, lungs, plasma assayed using an immune monitoring 48-plex panel. results showed significantly dysregulated cytokine, chemokine, growth factor concentrations compared time-matched controls, principally hearts, then lungs lesser extent, length with cortex largely unaffected. Major significant analytes contributing variance included eotaxin-1, IL-33, betacellulin, which generally downregulated across time. study suggest toxicity may persist from single have wide implications endurance expanding population

Language: Английский

Citations

0
Mu‐opioid receptors in tachykinin‐1‐positive cells mediate the respiratory and antinociceptive effects of the opioid fentanyl DOI Creative Commons

Andreea Furdui,

Carolina da Silveira Scarpellini, Gaspard Montandon

et al.

British Journal of Pharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 6, 2024

Abstract Background and Purpose Opioid drugs are potent analgesics that carry the risk of respiratory side effects due to actions on μ ‐opioid receptors (MORs) in brainstem regions control respiration. Substance P is encoded by Tac1 gene expressed neurons regulating breathing, nociception, locomotion. Tac1‐ positive cells also express MORs mediating opioid‐induced depression. We determined role ‐positive opioid drugs. Experimental Approach In situ hybridization was used determine Oprm1 mRNA expression (gene encoding MORs) depression Conditional knockout mice lacking functional were produced locomotor responses analgesic fentanyl assessed using whole‐body plethysmography. A tail immersion assay assess antinociceptive response fentanyl. Key Results highly (>80%) subpopulations preBötzinger Complex, nucleus tractus solitarius, Kölliker–Fuse/lateral parabrachial region. Conditionally knocking out abolished rate, relative tidal volume, minute ventilation compared with mice. Importantly, eliminated cells, whereas induced preserved. Conclusions Implications Our findings suggest mediate depressive fentanyl, providing important insights for development pain therapies reduced effects.

Language: Английский

Citations

0