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| http://dx.doi.org/10.3389/fphys.2023.1348910 | DOI Listing |
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Fentanyl enhances immune cell response through TLR4/MD-2 complex.
Front Pharmacol
October 2024
Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy.
Article Synopsis
- Fentanyl triggers neuroinflammation and immune activation through the TLR4/MD-2 complex, leading to side effects like tolerance and increased pain sensitivity.
- The study assessed fentanyl's effects on proinflammatory responses in rat microglia and human macrophages using techniques like real-time PCR and ELISA, while examining TLR4/MD-2 signaling pathways.
- Results showed fentanyl increases proinflammatory mediator levels and NF-κB activation linked to TLR4/MD-2, suggesting that targeting this pathway could enhance the safety and effectiveness of opioid pain management.
The epigenetic signatures of opioid addiction and physical dependence are prevented by D-cysteine ethyl ester and betaine.
Front Pharmacol
August 2024
Department of Biological Sciences, Kent State University, Kent, OH, United States.
We have reported that D,L-thiol esters, including D-cysteine ethyl ester (D-CYSee), are effective at overcoming opioid-induced respiratory depression (OIRD) in rats. Our on-going studies reveal that co-injections of D-CYSee with multi-day morphine injections markedly diminish spontaneous withdrawal that usually occurs after cessation of multiple injections of morphine in rats. Chronically administered opioids are known (1) to alter cellular redox status, thus inducing an oxidative state, and (2) for an overall decrease in DNA methylation, therefore resulting in the transcriptional activation of previously silenced long interspersed elements (LINE-1) retrotransposon genes.
View Article and Find Full Text PDFTropine exacerbates the ventilatory depressant actions of fentanyl in freely-moving rats.
Front Pharmacol
June 2024
Department of Pediatrics, Case Western Reserve University, Cleveland, OH, United States.
Our lab is investigating the efficacy profiles of tropine analogs against opioid-induced respiratory depression. The companion manuscript reports that the cell-permeant tropeine, tropine ester (Ibutropin), produces a rapid and sustained reversal of the deleterious actions of fentanyl on breathing, alveolar-arterial (A-a) gradient (i.e.
View Article and Find Full Text PDFOpioids and the Gastrointestinal Tract: The Role of Peripherally Active µ-Opioid Receptor Antagonists in Modulating Intestinal Permeability.
Am J Gastroenterol
October 2024
Mayo Clinic, Jacksonville, Florida, USA.
Opioid receptors are found throughout the gastrointestinal tract, including the large intestine. Many patients treated with opioids experience opioid-induced constipation (OIC). Laxatives are not effective in most patients, and in those who do initially respond, the efficacy of laxatives generally diminishes over time.
View Article and Find Full Text PDFFact vs. fiction: naloxone in the treatment of opioid-induced respiratory depression in the current era of synthetic opioids.
Front Public Health
March 2024
Tennessee Bureau of Investigation, Nashville, TN, United States.
Opioid-induced respiratory depression (OIRD) deaths are ~80,000 a year in the US and are a major public health issue. Approximately 90% of fatal opioid-related deaths are due to synthetic opioids such as fentanyl, most of which is illicitly manufactured and distributed either on its own or as an adulterant to other drugs of abuse such as cocaine or methamphetamine. Other potent opioids such as nitazenes are also increasingly present in the illicit drug supply, and xylazine, a veterinary tranquilizer, is a prevalent additive to opioids and other drugs of abuse.
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