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Recent Progress of Opioid Research, 2nd Edition

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: closed (20 November 2024) | Viewed by 5445

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Dr. Soichiro Ide

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Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
Interests: opioids; addiction; pain; depression; stress
Special Issues, Collections and Topics in MDPI journals

Dr. Kazutaka Ikeda

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Guest Editor

Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
Interests: dopamine; addiction; neuropsychopharmacology; genome; developmental disorders
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Dear Colleagues,

The endogenous opioid system plays a crucial role in the regulation of pain sensitivity and stress responses. In addition, many prescription opioids are typically prescribed to treat moderate to severe pain. Moreover, in addition to their advantageous properties as analgesics, prescription opioids exert a variety of side effects, including constipation and respiratory depression, as well as the formation of tolerance and dependence. Opioid use disorders caused by prolonged opioid use and overdose have become a major social problem in recent years. On the other hand, the detailed mechanisms of these effects and side effects, as well as the mechanisms of pain, dependence, and emotional regulation by endogenous opioids, remain unclear. In particular, most prescription opioid analgesics target the μ opioid receptor, but they also exert effects on the δ and κ subtypes; recently, the effects of subtypes other than μ have attracted attention and are being investigated as targets for analgesics and for the discovery of other drugs. In this Special Issue, we would like to highlight various recent studies related to opioids. In its Volume I, 12 papers were published. We sincerely encourage you to read these papers and welcome your contributions to Volume II.

Dr. Soichiro Ide
Dr. Kazutaka Ikeda
Guest Editors

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Keywords

opioids
opioid crisis
pain
analgesic
addiction
dependence
stress
reward
opioid peptides
opioid use disorder

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Published Papers (4 papers)

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Research

15 pages, 281 KiB

Open AccessArticle

TMEM132C rs7296262 Single-Nucleotide Polymorphism Is Significantly Associated with Nausea Induced by Opioids Administered for Cancer Pain and Postoperative Pain

by Yuna Kang, Daisuke Nishizawa, Seii Ohka, Takeshi Terui, Kunihiko Ishitani, Ryozo Morino, Miyuki Yokota, Junko Hasegawa, Kyoko Nakayama, Yuko Ebata, Kyotaro Koshika, Tatsuya Ichinohe and Kazutaka Ikeda

Int. J. Mol. Sci. 2024, 25(16), 8845; https://doi.org/10.3390/ijms25168845 - 14 Aug 2024

Viewed by 1011

Abstract

Opioids are almost mandatorily used for analgesia for cancer pain and postoperative pain. Opioid analgesics commonly induce nausea as a side effect. However, the genetic factors involved are still mostly unknown. To clarify the genetic background of individual differences in the occurrence of nausea during opioid administration, the incidence of nausea was investigated in 331 patients (Higashi-Sapporo Hospital [HS] group) who received morphine chronically for cancer pain treatment and in 2021 patients (Cancer Institute Hospital [CIH] group) who underwent elective surgery under general anesthesia. We conducted a genome-wide association study of nausea in HS samples. Among the top 20 candidate single-nucleotide polymorphisms (SNPs), we focused on the TMEM132C rs7296262 SNP, which has been reportedly associated with psychiatric disorders. The rs7296262 SNP was significantly associated with nausea in both the HS and CIH groups (TT+TC vs. CC; HS group, p = 0.0001; CIH group, p = 0.0064). The distribution of nausea-prone genotypes for the rs7296262 SNP was reversed between HS and CIH groups. These results suggest that the TMEM132C rs7296262 SNP is significantly associated with nausea during opioid use, and the effect of the SNP genotype on nausea is reversed between chronic and acute phases of opioid use. Full article

(This article belongs to the Special Issue Recent Progress of Opioid Research, 2nd Edition)

12 pages, 435 KiB

Open AccessArticle

OPRM1 Gene Polymorphism in Women with Alcohol Use Disorder

by Agnieszka Boroń, Aleksandra Suchanecka, Krzysztof Chmielowiec, Małgorzata Śmiarowska, Jolanta Chmielowiec, Aleksandra Strońska-Pluta, Remigiusz Recław and Anna Grzywacz

Int. J. Mol. Sci. 2024, 25(5), 3067; https://doi.org/10.3390/ijms25053067 - 6 Mar 2024

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Abstract

The main aims of the present study were to explore the relationship of the OPRM1 gene rs1074287 polymorphism in alcohol-dependent women with their personality traits and to try to find out whether any specific features may influence alcohol cravings and be a prognostic for alcohol dependency and treatment in AUD women. Our study found a notable correlation between openness and the interaction of the ORIM1 gene and AUD. The alcohol use disorder subjects with genotype AG showed a higher level of openness compared to the control group with genotypes AG (p = 0.0001) and AA (p = 0.0125). The alcohol use disorder subjects with the AA genotype displayed higher levels of openness than the control group with genotype AG (p = 0.0271). However, the alcohol use disorder subjects with the AA genotype displayed lower levels of openness than the control group with genotype GG (p = 0.0212). Our study indicates that openness as a personality trait is correlated with the OPRM1 gene rs1074287 polymorphism in alcohol-dependent women. These are the first data and results exploring such a relationship between opioid and alcohol pathways and the mental construction of AUD women. Personality traits such as openness to experience and neuroticism might play major roles in the addiction mechanism, especially in genetically predisposed females, independent of the reward system involved in the emotional disturbances that coexist with anxiety and depression. Full article

(This article belongs to the Special Issue Recent Progress of Opioid Research, 2nd Edition)

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19 pages, 3370 KiB

Open AccessArticle

The Role of Opioid Receptor Antagonists in Regulation of Blood Pressure and T-Cell Activation in Mice Selected for High Analgesia Induced by Swim Stress

by Dominik Skiba, Kinga Jaskuła, Agata Nawrocka, Piotr Poznański, Marzena Łazarczyk, Łukasz Szymański, Tymoteusz Żera, Mariusz Sacharczuk, Agnieszka Cudnoch-Jędrzejewska and Zbigniew Gaciong

Int. J. Mol. Sci. 2024, 25(5), 2618; https://doi.org/10.3390/ijms25052618 - 23 Feb 2024

Viewed by 1440

Abstract

Opioid peptides and their G protein-coupled receptors are important regulators within the cardiovascular system, implicated in the modulation of both heart and vascular functions. It is known that naloxone—an opioid antagonist—may exert a hypertensive effect. Recent experimental and clinical evidence supports the important role of inflammatory mechanisms in hypertension. Since opioids may play a role in the regulation of both blood pressure and immune response, we studied these two processes in our model. We aimed to evaluate the effect of selective and non-selective opioid receptor antagonists on blood pressure and T-cell activation in a mouse model of high swim stress-induced analgesia. Blood pressure was measured before and during the infusion of opioid receptor antagonists using a non-invasive tail–cuff measurement system. To assess the activation of T-cells, flow cytometry was used. We discovered that the non-selective antagonism of the opioid system by naloxone caused a significant elevation of blood pressure. The selective antagonism of μ and κ but not δ opioid receptors significantly increased systolic blood pressure. Subsequently, a brief characterization of T-cell subsets was performed. We found that the blockade of μ and δ receptors is associated with the increased expression of CD69 on CD4 T-cells. Moreover, we observed an increase in the central memory CD4 and central memory CD8 T-cell populations after the δ opioid receptor blockade. The antagonism of the μ opioid receptor increased the CD8 effector and central memory T-cell populations. Full article

(This article belongs to the Special Issue Recent Progress of Opioid Research, 2nd Edition)

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15 pages, 4593 KiB

Open AccessArticle

Optimization of a Nucleophilic Two-Step Radiosynthesis of 6-O-(2-[¹⁸F]fluoroethyl)-6-O-desmethyl-diprenorphine ([¹⁸F]FE-DPN) for PET Imaging of Brain Opioid Receptors

by Enikő Németh, Barbara Gyuricza, Viktória Forgács, Paul Cumming, Gjermund Henriksen, János Marton, Beate Bauer, Pál Mikecz and Anikó Fekete

Int. J. Mol. Sci. 2023, 24(17), 13152; https://doi.org/10.3390/ijms241713152 - 24 Aug 2023

Cited by 1 | Viewed by 1284

Abstract

We have established a method for nucleophilic one-pot, two-step radiosynthesis of the popular opioid receptor radioligand 6-O-(2-[¹⁸F]fluoroethyl)-6-O-desmethyl-diprenorphine ([¹⁸F]FE-DPN) from the novel precursor 6-O-(2-tosyloxyethyl)-6-O-desmethyl- 3-O-trityl-diprenorphine (TE-TDDPN), which we designate as the Henriksen precursor. We undertook an optimization of the synthesis conditions, aiming to enhance the accessibility of [¹⁸F]FE-DPN for positron emission tomography (PET) studies of μ-opioid receptors. Herein, we report an optimized direct nucleophilic ¹⁸F-fluorination and the deprotection conditions for a fully automated radiosynthesis of [¹⁸F]FE-DPN on a modified GE Tracerlab FX FE synthesis panel. Starting from 1–1.5 GBq of [¹⁸F]fluoride and applying an Oasis Max 1cc cartridge for fluorine-18 trapping with a reduced amount of K₂CO₃ (5.06 μmol K⁺ ion), [¹⁸F]FE-DPN ([¹⁸F]11) was produced with 44.5 ± 10.6 RCY (decay-corrected), high radiochemical purity (>99%), and a molar activity of 32.2 ± 11.8 GBq/μmol in 60–65 min. Full article

(This article belongs to the Special Issue Recent Progress of Opioid Research, 2nd Edition)

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