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The exceedingly large genus Euphorbia is broadly distributed in all phytogeographical units and various habitats all over Iran. Iranian Traditional Medicine has referred to a variety of its biological properties, including pain alleviation. This study aimed to investigate the antinociceptive activity of four Iranian endemic Euphorbia species (E. malleata, E. gypsicola, E. caspica, and E. sylvicola) for the first time. We used two pharmacological pain tests; tail-flick and writhing tests in mice. E. malleata showed the best effect among the species and was selected for further studies. The antinociceptive effects of different fractions of the methanolic extract of E. malleata were analyzed using the tail-flick test. The ethyl acetate fraction showed the highest antinociceptive activity and was selected for phytochemical analysis. This led to the isolation of six compounds, including oleanolic acid (1), methyl gallate (2), scopoletin (3), (2 S)-5,7,3′,5′-tetrahydroxyflavanone (4), (-)-catechin (5), and hyperoside (6). The structures of the compounds were identified by NMR and mass spectrometry. In addition, the antinociceptive activities of the compounds were assessed by the tail-flick test. Compounds 4 and 6 , which have flavonoid structures, showed the best antinociceptive effects with ED 50 values of 5.0 and 4.9 mg/kg, respectively. Pretreatment with naloxone (an opioid antagonist) attenuated the antinociceptive effects of each isolated compound in the tail-flick test. The molecular docking study showed that compound 6 had the best interaction with the active site of the mu-opioid receptor (5C1M). Based on findings, it can be concluded that E. malleata has antinociceptive effects. The reduction of the antinociceptive effect of the isolated compounds by naloxone, as well as the affinity for binding to the active site of mu receptor in docking study, suggest that opioid receptors may be involved in the antinociceptive effect. [Display omitted] • Four Iranian Euphorbia species showed the dose-dependent antinociceptive activity. • Euphorbia malleata was the most effective species. • Analysis of the ethyl acetate fraction led to the isolation of 6 compounds. • Hyperoside showed the most antinociceptive activity. • Hyperoside had the best interaction with mu opioid receptor in docking study. [ABSTRACT FROM AUTHOR]

Unsuccessful anesthesia often occurs under an inflammatory tissue environment, making dentistry treatment extremely painful and challenging. Articaine (ATC) is a local anesthetic used at high (4%) concentrations. Since nanopharmaceutical formulations may improve the pharmacokinetics and pharmacodynamics of drugs, we encapsulated ATC in nanostructured lipid carriers (NLCs) aiming to increase the anesthetic effect on the inflamed tissue. Moreover, the lipid nanoparticles were prepared with natural lipids (copaiba (Copaifera langsdorffii) oil and avocado (Persia gratissima) butter) that added functional activity to the nanosystem. NLC-CO-A particles (~217 nm) showed an amorphous lipid core structure according to DSC and XDR. In an inflammatory pain model induced by λ-carrageenan in rats, NLC-CO-A improved (30%) the anesthetic efficacy and prolonged anesthesia (3 h) in relation to free ATC. In a PGE2-induced pain model, the natural lipid formulation significantly reduced (~20%) the mechanical pain when compared to synthetic lipid NLC. Opioid receptors were involved in the detected analgesia effect since their blockage resulted in pain restoration. The pharmacokinetic evaluation of the inflamed tissue showed that NLC-CO-A decreased tissue ATC elimination rate (ke) by half and doubled ATC's half-life. These results present NLC-CO-A as an innovative system to break the impasse of anesthesia failure in inflamed tissue by preventing ATC accelerated systemic removal by the inflammatory process and improving anesthesia by its association with copaiba oil. [ABSTRACT FROM AUTHOR]

Introduction: Genes often have multiple polymorphisms that interact with each other and the environment in different individuals. Variability in the opioid receptors can influence opiate withdrawal and dependence. In humans, A118G Single Nucleotide Polymorphisms (SNP) on µ-Opioid Receptor (MOR), 36 G>T in κ-Opioid Receptor (KOR), and T921C in the d-Opioid Receptor (DOR) have been found to associate with substance dependence. Methods: To investigate the association between opioid receptors gene polymorphism and heroin addiction, 100 control subjects with no history of opioid use, and 100 heroin addicts (50% males and 50% females) in Tehran (capital of Iran), were evaluated. A118G, 36 G>T, and T921C SNPs on the MOR, KOR, DOR genes, respectively, were genotyped by sequencing. Results: We found no differences in either allele or genotype frequency for MOR, KOR and DOR genes SNPs between controls and subjects addicted to heroin. Conclusion: The relationships among polymorphisms may be important in determining the risk profile for complex diseases such as addiction, but opioid addiction is a multifactorial syndrome which is partially hereditary and partially affected by the environment. [ABSTRACT FROM AUTHOR]

Background: Given the increasing number of lead poisoning in opioids users and since no study has been conducted so far to review lead poisoning in methamphetamine (crystal) users, this study aimed to investigate blood lead level in methamphetamine addicts.Methods: This study was conducted on 20 patients with methamphetamine poisoning and their blood lead level was measured. The subjects were selected from among patients with a history of continuous use of methamphetamine, without a history of using opiates in the past 6 months confirmed by a negative urine tests, and without a history of heavy metal poisoning.Results: Of all, 18 patients were male and the mean age was 32 ± 10 years; 17 patients were abusing the drug via inhalation and three persons via oral administration. The mean blood lead level was 2.3 ± 1.1 μg/dL and poisoning was not observed in any of the cases. Blood lead level was not associated with age, sex, dosage, and route of administration.Conclusion: Although blood lead level was not at poisoning level in people who only used methamphetamine in Iran, due to the simultaneous use of other substances and because of non-specific symptoms, lead poisoning must be suspected in all cases of substances poisoning. [ABSTRACT FROM AUTHOR]