Area tempestas (AT) is a forebrain area involved in the genesis and generalization of clonic convulsions in rats. This study reports that upon AT application opiates and opioid peptides produce antinociceptive effects as measured with the hot-plate (HP) and tail-flick (TF) tests in rats. Unilateral infusion of mu and kappa agonists into AT at doses in the nanogram range delayed the latency to respond for the contralateral paws in the HP test (Emax, 67-91 degrees of analgesia), beginning 1 to 5 min after application. A smaller effect was observed after the Leu-enkephalin, [D-Ala2,D-Leu5][enkephalin and D-Pen2,D-Pen5]enkephalin. No effect was observed after Met-enkephalin. In the TF test, unilateral application of mu and kappa agonists in the nanogram range produced antinociception with Emax values of 43 to 62 degrees of analgesia, beginning 5 to 15 min after infusion. No significant effect was found after unilateral infusion of delta agonists. Infusion into AT (10 min before) of naltrexone (2-4 ng), ICI 154, 129 (1-10 ng) and WIN 44,441-3 (2-20 ng) antagonized the antinociception evoked by locally applied morphine (25 ng), [D-Pen2,D-Pen5]enkephalin (50 ng) and U 50,488 (100 ng), respectively. In addition, antinociception induced by systemic morphine (2.5 mg/kg sc) was antagonized by subsequent (23 min) unilateral application of naltrexone (15 ng). In the HP test, a reduction of the antinociceptive effect of morphine was obtained for both ipsilateral and contralateral paws after the antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)
Download full-text PDF |
Source |
---|
Elife
January 2025
Department of Pharmaceutical Sciences, University of Kentucky, Lexington, United States.
Reversing opioid overdoses in rats using a drug that does not enter the brain prevents the sudden and severe withdrawal symptoms associated with therapeutics that target the central nervous system.
View Article and Find Full Text PDFInt J Epidemiol
December 2024
Program in Addiction Medicine, Yale School of Medicine, New Haven, CT, United States.
Observational studies play an increasingly important role in estimating causal effects of a treatment or an exposure, especially with the growing availability of routinely collected real-world data. To facilitate drawing causal inference from observational data, we introduce a conceptual framework centered around "four targets"-target estimand, target population, target trial, and target validity. We illustrate the utility of our proposed "four targets" framework with the example of buprenorphine dosing for treating opioid use disorder, explaining the rationale and process for employing the framework to guide causal thinking from observational data.
View Article and Find Full Text PDFBiostatistics
December 2024
Department of Statistical Sciences, College of Arts and Sciences, Wake Forest University, 127 Manchester Hall, Winston-Salem, NC, 27109, United States.
The opioid epidemic is a significant public health challenge in North Carolina, but limited data restrict our understanding of its complexity. Examining trends and relationships among different outcomes believed to reflect opioid misuse provides an alternative perspective to understand the opioid epidemic. We use a Bayesian dynamic spatial factor model to capture the interrelated dynamics within six different county-level outcomes, such as illicit opioid overdose deaths, emergency department visits related to drug overdose, treatment counts for opioid use disorder, patients receiving prescriptions for buprenorphine, and newly diagnosed cases of acute and chronic hepatitis C virus and human immunodeficiency virus.
View Article and Find Full Text PDFCancer
February 2025
Department of Palliative, Rehabilitation and Integrative Medicine, The University of Texas MD Anderson Cancer, Houston, Texas, USA.
Background: There is much concern that opioids administered as intravenous (iv) bolus for pain relief may inadvertently increase their risk for abuse. However, there is insufficient data to support this. The authors compared the abuse liability potential, analgesic efficacy, and adverse effect profile of fast (iv push) versus slow (iv piggyback) administration of iv hydromorphone among hospitalized patients requiring iv opioids for pain.
View Article and Find Full Text PDFPharmaceuticals (Basel)
January 2025
Department of Biotechnology and Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.
There is clinical concern about the combined use of alcohol and opiates. Several lines of evidence support an interaction between alcohol and the endogenous opioid system. Thus, we hypothesized that ethanol, by causing the release of opioid peptides, may sensitize the system to the action of exogenous opioids such as morphine.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!