Article
Biochemistry & Molecular Biology
Alex Disney, Keith M. Olson, Amanda M. Shafer, Sierra C. Moore, Jessica P. Anand, John R. Traynor, Stephen M. Husbands
Summary: The study designed and synthesized an orvinol antagonist, 14, which showed no agonist activity in vitro, and was at least equally effective as naloxone in reversing the effects of mu-opioid receptor agonists in vivo.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Clinical Neurology
Eileen Nguyen, Kelly M. Smith, Nathan Cramer, Ruby A. Holland, Isabel H. Bleimeister, Krystal Flores-Felix, Hanna Silberberg, Asaf Keller, Claire E. Le Pichon, Sarah E. Ross
Summary: By using molecular, tracing, and behavioural approaches, Nguyen et al. discovered that neurons containing the kappa-opioid receptor in the rostral ventromedial medulla can robustly modulate itch and pain behaviours bidirectionally, shedding light on a distinct population of neurons that inhibit itch and nociception.
Review
Biochemistry & Molecular Biology
Zoe Li, Jie Liu, Fan Dong, Nancy Chang, Ruili Huang, Menghang Xia, Tucker A. Patterson, Huixiao Hong
Summary: The United States is facing a severe opioid crisis, with increasing numbers of deaths caused by both prescription and illegal opioids over the past two decades. Opioids are important for pain treatment but also highly addictive, making it difficult to combat this public health issue.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Andrea Cippitelli, Gilles Zribi, Lawrence Toll
Summary: PPL-103 has shown potential as a pharmacotherapy for the treatment of cocaine use disorder (CUD). It reduces self-administration of cocaine, decreases motivation for cocaine, and attenuates binge-like cocaine taking. PPL-103 also reduces priming- and cue-induced reinstatement of cocaine seeking. Tolerance development was not observed with repeated PPL-103 treatment.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2022)
Article
Pharmacology & Pharmacy
Xin Wang, Xiaoli Gou, Xiaojuan Yu, Dongdong Bai, Bowei Tan, Pingfeng Cao, Meilin Qian, Xiaoxiao Zheng, Hairong Wang, Pingming Tang, Chen Zhang, Fei Ye, Jia Ni
Summary: Kappa opioid receptor (KOR) agonists have potential for pain relief and treating pruritus, but their development is hindered by sedation, dysphoria and diuresis. The study on HSK21542 showed it to be a selective and potent KOR agonist with peripheral selectivity, providing a safe and effective alternative for patients suffering from pain and pruritus.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Wenjie Zhou, Yanhua Li, Xiaojing Meng, An Liu, Yu Mao, Xia Zhu, Qian Meng, Yan Jin, Zhi Zhang, Wenjuan Tao
Summary: This study indicates that anxiety is linked to different stages of pain, with DOR1 and DOR2 playing distinct roles in modulating excitatory pathways in the CeA. The findings suggest a functional switching of DOR1 and DOR2 associated with anxiety states at different stages of pain.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Neurosciences
Volker Neugebauer, Peyton Presto, Vadim Yakhnitsa, Nico Antenucci, Brianna Mendoza, Guangchen Ji
Summary: Neuroplasticity in cortico-limbic circuits is important in pain persistence and modulation. The amygdala plays a key role in the emotional dimension of pain, and interactions with prefrontal cortical regions change in pain conditions. Other regions in the limbic system are also involved in pain modulation. The corticolimbic system contains opioids and opioid receptors, and their modulatory effects and potential opposing functions are still not fully understood.
Article
Behavioral Sciences
Luke A. Jelen, James M. Stone, Allan H. Young, Mitul A. Mehta
Summary: This article reviews the dysregulation of the opioid system in depression and the potential of pharmacological modulators of mu, delta, and kappa opioid receptors for the treatment of depression. The review presents evidence from animal and clinical studies supporting the dysregulation of the opioid system in depression, the modulation of behavioral processes and brain regions associated with depression by opioids, and the modulation of antidepressant responses by opioids. The review also evaluates clinical trials examining the safety and efficacy of opioidergic agents in depression and explores the involvement of the opioid system in the effects of other treatments, such as ketamine, that exert antidepressant effects through non-opioid actions. Furthermore, the review explores the neurochemical and molecular mechanisms underlying the therapeutic effects of opioid system engagement, providing a rationale for further investigation into this relevant target in depression treatment.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2022)
Article
Medicine, Research & Experimental
Yongsheng Zhu, Kejia Wang, Tengfei Ma, Yuanyuan Ji, Yin Lou, Xiaoyu Fu, Ye Lu, Yige Liu, Wei Dang, Qian Zhang, Fangyuan Yin, Kena Wang, Bing Yu, Hongbo Zhang, Jianghua Lai, Yunpen Wang
Summary: This study identified neural pathways involved in controlling depressive-like behaviors and acute withdrawal symptoms after morphine withdrawal. Furthermore, a new DBS treatment protocol was developed to reverse abnormal plasticity and alleviate withdrawal symptoms and depressive-like behaviors.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Chemistry, Medicinal
Maree T. Smith, Dehui Kong, Andy Kuo, Mohammad Z. Imam, Craig M. Williams
Summary: The opioid crisis has increased the demand for novel opioid analgesics that have superior profiles compared to morphine. This Perspective reviews and discusses the multitargeted opioid ligand strategy for discovering such analgesics. Dual-targeted mu-opioid/delta-opioid (MOP/DOP) ligands with strong DOP antagonist potency and without DOP or kappa-opioid (KOP) agonist activity are promising candidates. Dual-targeted MOP/NOP partial agonists also show potential. The pharmacologic template of cebranopadol, a full agonist at MOP, DOP, and NOP receptors, and a partial agonist at KOP receptor, should be avoided due to its poor therapeutic indices.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Hongguang Ma, Huiqun Wang, James C. Gillespie, Rolando E. Mendez, Dana E. Selley, Yan Zhang
Summary: This study reported the application of a nitrogen-walk approach in developing novel opioid ligands, showing that introducing a nitrogen atom can maintain excellent binding affinity and induce a functional switch at the MOR. Computational investigations provided supportive evidence and explanations for the in vitro results, contributing to the rational design of low efficacy MOR ligands for opioid use disorder therapeutics.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Multidisciplinary Sciences
Shijia Liu, Dong-Il Kim, Tae Gyu Oh, Gerald M. Pao, Jong-Hyun Kim, Richard D. Palmiter, Matthew R. Banghart, Kuo-Fen Lee, Ronald M. Evans, Sung Han
Summary: Neurons expressing the mu-opioid receptor within the lateral parabrachial nucleus play a crucial role in opioid-induced respiratory depression (OIRD). Chemogenetic modulation of these neurons can rescue respiratory rhythms and serve as a potential therapeutic target for treating OIRD in patients.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Behavioral Sciences
Sally L. Huskinson, Donna M. Platt, C. Austin Zamarripa, Kristen Dunaway, Morgan Brasfield, Thomas E. Prisinzano, Bruce E. Blough, Kevin B. Freeman
Summary: KOR agonists have potential as treatments for pain, itch, and substance-use disorders, but typical KOR agonists have side effects. This study found that biased KOR agonists have fewer and milder side effects compared to typical KOR agonists. Additionally, the combination of KOR and MOR agonists resulted in different behavioral effects.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2022)
Article
Pharmacology & Pharmacy
Keith M. Olson, Andrea L. Devereaux, Payal Chatterjee, Savanah L. Saldana-Shumaker, Amanda Shafer, Adam Plotkin, Ram Kandasamy, Alexander D. MacKerell, John R. Traynor, Christopher W. Cunningham
Summary: This study investigates the structure-activity relationships of benzylideneoxymorphone analogs in order to develop analgesics with reduced tolerance and side effects. One compound, nitro-BOM (NBOM), showed high-efficacy antinociception but also exhibited tolerance and toxicity upon repeated administration. Despite these issues, NBOM provides an important tool for understanding MOPr/DOPr pharmacology.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Clinical Neurology
Neel Mehta, Neal E. Slatkin, Robert J. Israel, Nancy Stambler, Eric D. Shah
Summary: This study evaluated the safety and efficacy of methylnaltrexone in constipated patients and found that methylnaltrexone significantly improved rescue-free laxation. Abdominal pain was more common in patients receiving methylnaltrexone.
JOURNAL OF PAIN RESEARCH
(2023)
Review
Dermatology
S. Staender, G. Yosipovitch
BRITISH JOURNAL OF DERMATOLOGY
(2019)
Article
Dermatology
K. Agelopoulos, F. Ruelander, J. Dangelmater, T. Lolls, N. Osada, D. Metze, T. A. Luger, K. Loser, S. Staender
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2019)
Article
Dermatology
L. Misery, E. Weisshaar, E. Brenaut, A. W. M. Evers, F. Huet, S. Staender, A. Reich, E. Berardesca, E. Serra-Baldrich, J. Wallengren, D. Linder, J. W. Fluhr, J. C. Szepietowski, H. Maibach, Golara Honari, Christelle Le Gall-Ianotto, Kenji Takamori, Renee Richters
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2020)
Article
Dermatology
M. P. Pereira, L. Derichs, G. Meyer Zu Hoerste, K. Agelopoulos, S. Staender
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2020)
Article
Medicine, General & Internal
Bruno Vincenzi, Mike Trower, Ajay Duggal, Pamela Guglielmini, Peter Harris, David Jackson, Mario E. Lacouture, Emiliangelo Ratti, Giuseppe Tonini, Andrew Wood, Sonja Staender
Article
Dermatology
M. Augustin, C. Garbe, K. Hagenstroem, J. Petersen, M. P. Pereira, S. Staender
Summary: This retrospective healthcare research study on prurigo and pruritus in Germany revealed that prurigo is a relatively rare but significant disease, while pruritus is frequent and very variable in appearance. Both conditions have a high comorbidity burden, with common comorbidities including hypertension, hyperlipidaemia, and depression.
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2021)
Article
Dermatology
Christina Schut, Florence J. Dalgard, Anthony Bewley, Andrea W. M. Evers, Uwe Gieler, Lars Lien, Francesca Sampogna, Sonja Staender, Lucia Tomas-Aragones, Nienke Vulink, Andrew Y. Finlay, Franz J. Legat, Geraldine Titeca, Gregor B. Jemec, Laurent Misery, Csanad Szabo, Vesna Grivcheva-Panovska, Saskia Spillekom-van Koulil, Flora Balieva, Jacek C. Szepietowski, Adam Reich, Barbara Roque Ferreira, Andrey Lvov, Dmitry Romanov, Servando E. Marron, Tamara Gracia-Cazana, Ake Svensson, Ilknur K. Altunay, Andrew R. Thompson, Claudia Zeidler, Joerg Kupfer
Summary: This study found that BDD symptoms were fivefold more prevalent in dermatological patients than in healthy skin controls, and were associated with young age, female sex, psychological stress, and feelings of stigmatization. Certain patient groups had a significantly higher chance of BDD symptoms compared with controls. Doctors should consider BDD more often in patients with dermatological conditions and refer them when necessary for assessment and treatment.
BRITISH JOURNAL OF DERMATOLOGY
(2022)
Article
Dermatology
M. Dehghan Nayyeri, M. Missler, R. Ritterbach, B. Sundermann, N. Wulms, A. Sueer, M. Dugas, M. P. Pereira, S. Staender, M. Schmelz, B. Pfleiderer
Summary: This study found decreased functional connectivity within the DMN in patients with BRP during rest. In contrast, there were no significant differences in functional connectivity at rest between AD patients and healthy controls.
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2022)
Article
Dermatology
Konstantin Agelopoulos, Lina Renkhold, Henning Wiegmann, Martin Dugas, Aysenur Suer, Claudia Zeidler, Martin Schmelz, Manuel P. Pereira, Sonja Staender
Summary: This study aimed to link gene expression, DNA methylation, and neuroanatomy in different chronic pruritis conditions. Results showed that specific signatures of gene expression and DNA methylation distinguished pruritic lesional skin from nonpruritic skin and healthy skin. Neuroanatomy analysis revealed differential branching patterns among the different conditions, indicating that chronic itching conditions are primarily caused by nerve injury and subsequent sprouting, while genuine neuropathy is expected in brachioradial pruritus.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Letter
Dermatology
Claudia Zeidler, Manuel P. Pereira, Sonja Stander
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2023)
Letter
Dermatology
Konstantin Agelopoulos, Sonja Staender
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Letter
Dermatology
Henning Wiegmann, Sonja Stander, Svetlan Bobko, Lina Renkhold, Tobias Lotts, Claudia Zeidler, Manuel Pereira, Konstantin Agelopoulos
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Gil Yosipovitch, Nicholas Mollanazar, Sonja Staender, Shawn G. Kwatra, Brian S. Kim, Elizabeth Laws, Leda P. Mannent, Nikhil Amin, Bolanle Akinlade, Heribert W. Staudinger, Naimish Patel, George D. Yancopoulos, David M. Weinreich, Sheldon Wang, Genming Shi, Ashish Bansal, John T. O'Malley
Summary: Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by intensely itchy nodules. The use of Dupilumab, a monoclonal antibody, has been shown to effectively improve itch and skin lesions in patients with PN.
Article
Dermatology
Sonja Staender, Fatoumata Fofana, Carla Dias-Barbosa, Danielle Rodriguez, Ismail Budhiarso, Zarif K. Jabbar-Lopez, Christophe Piketty, Margaret Vernon, Jorge Puelles
Summary: Patients with prurigo nodularis often have sleep disturbances due to itchy skin in the evening and at night. This study evaluates the Sleep Disturbance Numerical Rating Scale (SD NRS) as a tool for measuring sleep in prurigo nodularis patients. Results show that the SD NRS is easy to use and can be useful for assessing sleep on a daily basis.
DERMATOLOGY AND THERAPY
(2023)
Article
Dermatology
Gil Yosipovitch, Melinda J. Gooderham, Sonja Staender, Luz Fonacier, Jacek C. Szepietowski, Mette Deleuran, Giampiero Girolomoni, John C. Su, Andrew G. Bushmakin, Joseph C. Cappelleri, Claire Feeney, Gary Chan, Andrew J. Thorpe, Hernan Valdez, Pinaki Biswas, Ricardo Rojo, Marco Dibonaventura, Daniela E. Myers
Summary: This study examined the relationships among itch, sleep, and work productivity in patients with atopic dermatitis. The results showed that reducing itch severity is associated with improvements in sleep and work productivity, supporting the effectiveness of Abrocitinib in treating atopic dermatitis.
AMERICAN JOURNAL OF CLINICAL DERMATOLOGY
(2023)
