Article
Behavioral Sciences
Feng Li, Yanling Qiao, Yuanyuan Chen, Nan Li, Mengxiang Yang, Xiangyu Li, Yi Qiu, Wei Cui, Haowei Shen, Peng Xu, Bin Di
Summary: This study compared the anesthetic, analgesic activity, and abuse liability of the new synthetic drug N-Ethylnorketamine (NENK) with ketamine. The results showed that NENK has lower anesthetic and analgesic activity compared to ketamine, but has significant abuse liability.
BEHAVIOURAL BRAIN RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Jayane Lais Dias Quintao, Amanda Cristina Reis Gonzaga, Giovane Galdino, Thiago Roberto Lima Romero, JosianeFernandes Silva, VirginiaSoares Lemos, Gabriel Henrique Campolina-Silva, Cleida Aparecida de Oliveira, GermanAnarturo Bohorquez Mahecha, IgorDimitri Gama Duarte
Summary: Tissue injury leads to the release of inflammatory mediators and nociceptive substances, contributing to hyperalgesia. The study investigated the involvement of inflammatory mediators in the modulation of inflammatory pain by the opioid system, finding that TNF-alpha, CXCL-1, and IL-beta cause hyperalgesia and the release of endogenous opioid peptides for pain control.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Neurosciences
R. Ross MacLean, Elise E. DeVito, Tore Eid, Suprit Parida, Ralitza Gueorguieva, Mehmet Sofuoglu
Summary: This study used a novel double-blind placebo-controlled intravenous nicotine self-administration model to determine the threshold for detecting positive effects of nicotine in young adult smokers. The results showed that a dose of about 0.1 mg of nicotine was needed to detect positive effects, while a higher dose of 0.2 mg was required to produce consistent nicotine reinforcement. These findings support the value of nicotine reinforcement threshold as a tobacco regulatory target.
PSYCHOPHARMACOLOGY
(2021)
Article
Behavioral Sciences
Michael T. Sapko, Taleen Hanania, Qing Chang, Jonathan C. Javitt
Summary: This study aimed to evaluate the abuse liability of D-cycloserine (DCS) using a self-administration paradigm. The results showed that DCS did not result in self-administration at any of the test doses and had similar behavior to the control group.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2023)
Article
Neurosciences
Cynthia A. A. Crawford, Jordan A. A. Taylor, Ginny I. I. Park, Jasmine W. W. Rios, Joseph Bunch, Constance J. J. Greenwood, David Y. Lopez Y. Sanchez, Diego J. J. Gonzales
Summary: This study examined the effects of early fentanyl exposure on adolescent fentanyl self-administration and opioid-mediated thermal antinociception in rats. The results showed that early fentanyl exposure altered thermal antinociception in both male and female rats, and females were more susceptible to fentanyl abuse.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Chemistry, Medicinal
Ramajayam Kuppusamy, Ying-Ting Hsu, Yi-Yu Ke, Po-Wei Chang, Yung-Chiao Chang, Hsiao-Fu Chang, Pei-Chen Wang, Yu-Hao Lin, Yu-Chen Huang, Teng-Kuang Yeh, Jian-Ying Chuang, Horace H. Loh, Chuan Shih, Chiung-Tong Chen, Shiu-Hwa Yeh, Shau-Hua Ueng
Summary: This study modified the structure of a previously identified compound and discovered a new, potent analgesic with reduced side effects. The analgesic activated mu-opioid receptors through specific signaling pathways and showed weak effects on other related receptors. It exhibited strong antinociception in pain and allodynia models with less gastrointestinal inhibition and tolerance compared to morphine.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Pediatrics
William T. Basco, Jenna L. McCauley, Jingwen Zhang, Patrick D. Mauldin, Kit N. Simpson, Khosrow Heidari, Justin E. Marsden, Sarah J. Ball
Summary: Over an 8-year period, the rate of opioid analgesic prescriptions dispensed to children aged 0 to 18 in South Carolina decreased by 35.6%, with minimal decline in the mean daily morphine milligram equivalents (MMEs) dispensed per day, especially for children aged 0 to 9.
Article
Pharmacology & Pharmacy
Caroline A. Arout, Margaret Haney, Evan S. Herrmann, Gillinder Bedi, Ziva D. Cooper
Summary: This study found that acute oral CBD did not consistently demonstrate dose-dependent analgesic effects in healthy noncannabis users, and in fact increased pain in some measures. Future studies should consider using more comprehensive pain assessment paradigms and investigate the analgesic effects of CBD in different populations.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Katarzyna Kaczynska, Piotr Wojciechowski
Summary: Opioids, while potent analgesics, are associated with side effects like tolerance, addiction, respiratory depression, and cardiovascular events. Researchers are seeking ways to counteract these effects, with peptides and related compounds showing potential in modulating opioid actions. Various peptides, including nociceptin/orphanin, ghrelin, oxytocin, endothelin, and venom peptides, have been researched for their modulation of opioid effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Jill A. Rabinowitz, Jin Jin, Sally I-Chun Kuo, Adrian Campos, Miguel E. Renteria, Andrew S. Huhn, Johannes Thrul, Beth A. Reboussin, Kelly Benke, Benjamin Domingue, Nicholas S. Ialongo, Brion S. Maher, Darlene Kertes, Vanessa Troiani, George Uhl
Summary: This study examined the association between polygenic risk scores (PRS) for lifetime cannabis and alcohol use and the misuse of opioids among an urban, African-American sample. The findings suggest that higher PRS for lifetime cannabis use, heavy drinking, and alcohol consumption are associated with an increased risk for opioid misuse. Additionally, there are significant sex differences in these associations.
Review
Behavioral Sciences
Celian Bertin, Noemie Delage, Benjamin Rolland, Lucie Pennel, Melina Fatseas, Anne-Priscille Trouvin, Jessica Delorme, Chouki Chenaf, Nicolas Authier
Summary: Chronic pain often results in opioid prescriptions, leading to addiction issues especially in high-risk patients with comorbidities. Managing pain in dependent patients is complex and yet to be established. An integrative review proposed definitions, strategies, and guidelines for holistic management in multi-comorbid patients.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2021)
Article
Medicine, General & Internal
Marcus A. Bachhuber, Denis Nash, William N. Southern, Moonseong Heo, Matthew Berger, Mark Schepis, Manu Thakral, Chinazo O. Cunningham
Summary: This study assessed the impact of modifying opioid analgesic prescribing defaults in the electronic health record (EHR) by reducing the default dispense quantity to 10 tablets. Results showed a decrease in the quantity prescribed initially, but no significant increase in health service use within 30 days. Overall, reducing EHR default dispense quantities for opioid analgesics is a feasible strategy that may modestly reduce prescribing.
Article
Biochemistry & Molecular Biology
Lisa M. Eubanks, Steven Blake, Yoshihiro Natori, Beverly Ellis, Paul T. Bremer, Kim D. Janda
Summary: The opioid epidemic remains a dire public health crisis, with synthetic opioids such as fentanyl being highly potent and dangerous. Researchers have developed vaccines targeting synthetic opioids like fentanyl and carfentanil, which have shown protective effects in mice, providing new strategies for preventing drug abuse and overdose.
ACS CHEMICAL BIOLOGY
(2021)
Article
Chemistry, Medicinal
Edin Muratspahic, Natasa Tomasevic, Johannes Koehbach, Leopold Duerrauer, Seid Hadzic, Joel Castro, Gudrun Schober, Spyridon Sideromenos, Richard J. Clark, Stuart M. Brierley, David J. Craik, Christian W. Gruber
Summary: The escalating opioid crisis, driven by the abuse of prescription opioids, has become a global societal and public health burden. Developing novel pain medications using sunflower-derived compounds has shown promise in treating chronic abdominal pain without central side effects.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Nutrition & Dietetics
Vicente Agullo, Maria Eva Gonzalez-Trujano, Alberto Hernandez-Leon, Erika Estrada-Camarena, Francisco Pellicer, Cristina Garcia-Viguera
Summary: This study aimed to investigate the analgesic properties of a lyophilized obtained from a newly designed maqui-citrus beverage alone and combined with different sweeteners. The results showed that the combination of maqui and citrus had beneficial effects in relieving pain, while the presence of sweeteners could reduce or avoid this effect.
Review
Chemistry, Medicinal
Norikazu Kiguchi, Huiping Ding, Shiroh Kishioka, Mei-Chuan Ko
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2020)
Review
Neurosciences
Norikazu Kiguchi, Huiping Ding, Mei-Chuan Ko
Summary: This article discusses the functional profiles of ligands with dual NOP and MOP receptor agonist activities and highlights their advantages in pain relief and drug abuse treatment. By coactivating NOP and MOP receptors, these ligands demonstrate a wider therapeutic window and fewer side effects.
JOURNAL OF NEUROSCIENCE RESEARCH
(2022)
Article
Cell Biology
Santosh K. Mishra, Joshua J. Wheeler, Saumitra Pitake, Huiping Ding, Changyu Jiang, Tomoki Fukuyama, Judy S. Paps, Patrick Ralph, Jacob Coyne, Michelle Parkington, Jennifer DeBrecht, Lauren C. Ehrhardt-Humbert, Glenn P. Cruse, Wolfgang Baeumer, Ru-Rong Ji, Mei-Chuan Ko, Thierry Olivry
Article
Multidisciplinary Sciences
Christopher R. Donnelly, Changyu Jiang, Amanda S. Andriessen, Kaiyuan Wang, Zilong Wang, Huiping Ding, Junli Zhao, Xin Luo, Michael S. Lee, Yu L. Lei, William Maixner, Mei-Chuan Ko, Ru-Rong Ji
Summary: STING is a critical immune regulator that induces type-I interferons and other cytokines to promote immune-cell-mediated clearance of pathogens and neoplastic cells. STING also plays a role in antitumour immunity and has potential as a target for cancer immunotherapy. Additionally, STING is shown to regulate nociception through IFN-I signaling, leading to pain relief in mice and non-human primates.
Article
Cell Biology
Eileen Nguyen, Grace Lim, Huiping Ding, Junichi Hachisuka, Mei-Chuan Ko, Sarah E. Ross
Summary: The study found that morphine-induced itch is caused by neurons rather than mast cells, and spinal dynorphin neurons play an important role in mice. Agonism of the kappa-opioid receptor can alleviate morphine-induced itch, challenging the long-standing use of antihistamines.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Review
Neurosciences
Huiping Ding, Mei-Chuan Ko
Summary: NHP models have been instrumental in opioid research for over five decades, offering more accurate conclusions in areas such as analgesia, abuse liability, and respiratory depression. Recent studies suggest that mixed mu opioid and nociceptin/orphanin FQ peptide receptor partial agonists may serve as safe, non-addictive analgesics.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Gastroenterology & Hepatology
Yong Chen, Zi-Long Wang, Michele Yeo, Qiao-Juan Zhang, Ana E. Lopez-Romero, Hui-Ping Ding, Xin Zhang, Qian Zeng, Sara L. Morales-Lazaro, Carlene Moore, Ying-Ai Jin, Huang-He Yang, Johannes Morstein, Andrey Bortsov, Marcin Krawczyk, Frank Lammert, Manal Abdelmalek, Anna Mae Diehl, Piotr Milkiewicz, Andreas E. Kremer, Jennifer Y. Zhang, Andrea Nackley, Tony E. Reeves, Mei-Chuan Ko, Ru-Rong Ji, Tamara Rosenbaum, Wolfgang Liedtke
Summary: The study identified LPC as a novel pruritogen in cholestatic liver diseases, causing itch through epithelia-sensory neuron cross talk. This finding provides a new perspective for the treatment of itch.
Article
Pharmacology & Pharmacy
Norikazu Kiguchi, Yohji Fukazawa, Ayano Saika, Daisuke Uta, Fumihiro Saika, Tomoe Y. Nakamura, Mei-Chuan Ko, Shiroh Kishioka
Summary: This study investigated the direct modulation of itch processing by central GRP(+) neurons in the CNS. The results suggest that central GRP(+) neurons play important roles in itch processing, with no significant sex differences observed, providing new insights for further research on the functional roles of itch-related neurons and the development of treatment strategies.
PHARMACOLOGY RESEARCH & PERSPECTIVES
(2021)
Article
Anesthesiology
Huiping Ding, Claudio Trapella, Norikazu Kiguchi, Fang-Chi Hsu, Girolamo Calo, Mei-Chuan Ko
Summary: Cebranopadol exhibits potent antinociceptive effects by mainly activating mu receptors in nonhuman primates, with reduced side effects including lack of respiratory depression and pruritus. Despite displaying decreased reinforcing strength compared to fentanyl, caution is warranted due to detectable reinforcing effects, emphasizing the importance of careful development and clinical use of cebranopadol.
Article
Pharmacology & Pharmacy
Sun H. Park, Matthew R. Eber, Miriam M. Fonseca, Chirayu M. Patel, Katharine A. Cunnane, Huiping Ding, Fang-Chi Hsu, Christopher M. Peters, Mei-Chuan Ko, Roy E. Strowd, John A. Wilson, Wesley Hsu, E. Alfonso Romero-Sandoval, Yusuke Shiozawa
Summary: Abnormal growth of sensory nerves contributes to cancer-related pain. Primary neuronal cultures from DRG are commonly used to study pain signaling. In this study, DRG sensory neurons from different species were established in serum-free conditions and showed altered neurite growth in response to cancer-derived factors and chemotherapeutic agents. Furthermore, a quantification method was developed to measure neurite length accurately and efficiently. Exogenous factors also affected gene expression in sensory neurons.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Neurosciences
Xin Luo, Ouyang Chen, Zilong Wang, Sangsu Bang, Jasmine Ji, Sang Hoon Lee, Yul Huh, Kenta Furutani, Qianru He, Xueshu Tao, Mei-Chuan Ko, Andrey Bortsov, Christopher R. Donnelly, Yong Chen, Andrea Nackley, Temugin Berta, Ru-Rong Ji
Summary: The IL-23/IL-17A/TRPV1 axis regulates female-specific mechanical pain, with IL-23 inducing pain in females but impaired in mice lacking IL-23 or IL-23r. IL-23-induced pain is promoted by estrogen and suppressed by androgen.
Article
Pharmacology & Pharmacy
Norikazu Kiguchi, Huiping Ding, Sun H. Park, Kelsey M. Mabry, Shiroh Kishioka, Yusuke Shiozawa, E. Alfonso Romero-Sandoval, Christopher M. Peters, Mei-Chuan Ko
Summary: This study aimed to compare the expression patterns of neuromedin B (NMB) and its receptor (NMBR) and the effects of NMB and gastrin-releasing peptide (GRP) on itch and pain in non-human primates (NHPs). The results showed that the NMB-NMBR system has minimal functional role in itch and pain neurotransmission in primates, while GRP elicited significant scratching responses. Drugs targeting the spinal NMB-NMBR system may not effectively alleviate non-NMBR-mediated itch.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Behavioral Sciences
Chang-Ming Chen, Huiping Ding, Kelsey M. Mabry, Mei-Chuan Ko
Summary: This study compared the antidepressant-like effects of a delta opioid receptor (DOR) agonist, SNC80, and a tricyclic antidepressant, amitriptyline, in rats under normal or inflammatory pain state. The results showed that the potency of SNC80-induced antidepressant-like effects, but not amitriptyline, was enhanced in rats under inflammatory pain. This suggests that DOR agonists may be more effective as potential antidepressants for patients experiencing both depression and pain.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2022)
Article
Neurosciences
Huiping Ding, Norikazu Kiguchi, Kelsey M. Mabry, Shiroh Kishioka, Mei-Chuan Ko
Summary: In nonhuman primates, opioids and cannabinoids have comparable analgesic effects, but only opioids cause physical dependence at their analgesic doses.
Review
Pharmacology & Pharmacy
Huiping Ding, Norikazu Kiguchi, MaryBeth Dobbins, E. Alfonso Romero-Sandoval, Shiroh Kishioka, Mei-Chuan Ko
Summary: As currently available opioid analgesics often have dose-limiting adverse effects, new approaches have been pursued to develop safe and non-addictive pain medications. NOP receptor-related agonists have emerged as a promising target for developing novel opioids that modulate the analgesic and addictive properties of MOP receptor agonists. Several lines of evidence suggest that peptidic and non-peptidic NOP receptor agonists and mixed NOP/MOP receptor partial agonists show potent analgesic effects in experimental animal models without eliciting adverse effects.
