Article
Anesthesiology
Elaine F. Toniolo, Achla Gupta, Adriano C. Franciosi, Ivone Gomes, Lakshmi A. Devi, Camila S. Dale
Summary: The interaction between CB1R and opioid receptors may be targeted for the treatment of diabetic neuropathy. CB1R-MOR and CB1R-DOR complexes are involved in diabetic neuropathy, and the peptide endocannabinoid hemopressin shows potential as a therapeutic for this condition.
Review
Biochemistry & Molecular Biology
Kornel Kiraly, David A. Karadi, Ferenc Zador, Amir Mohammadzadeh, Anna Rita Galambos, Mihaly Balogh, Pal Riba, Tamas Tabi, Zoltan S. Zadori, Eva Szoko, Susanna Furst, Mahmoud Al-Khrasani
Summary: There is ongoing debate on the effectiveness of opioids in the management of neuropathic pain, with dose escalation required to maintain analgesia leading to increased side effects. Literature suggests that angiotensin and its receptors may have an impact on pain transmission. The interaction between MOR and angiotensin receptors remains understudied in chronic pain, particularly neuropathy.
Article
Neurosciences
Dominika Labuz, Melih O. Celik, Viola Seitz, Halina Machelska
Summary: Interleukin-4 (IL-4) is an anti-inflammatory cytokine that can alleviate pain by releasing opioid peptides from infiltrating macrophages at injured nerves. This newly discovered mechanism involves PKA-mediated, PI3K-mediated, ryanodine receptor-mediated, and intracellular Ca21-mediated release from M1 macrophages of opioid peptides, which activate peripheral opioid receptors in injured tissue. Targeting the IL-4-opioid system in peripheral damaged tissue may offer a potential therapeutic approach with fewer central and systemic side effects.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Bi-Xin Zheng, Ayma Malik, Ming Xiong, Alex Bekker, Yuan-Xiang Tao
Summary: Neuropathic pain is a common clinical disorder that significantly impacts patient quality of life and imposes a substantial economic and social burden. Opioids are currently the last resort for treatment, but their effectiveness is limited due to downregulation of opioid receptors in primary afferent neurons after peripheral nerve trauma. Recent studies have shown that epigenetic modifications, transcription factor expression changes, and alterations in post-translational processing may contribute to this downregulation of opioid receptors in nerve trauma-related dorsal root ganglion neurons. Understanding these molecular mechanisms could offer new approaches for preventing or treating neuropathic pain.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Immunology
Xavier Mas-Orea, Lilian Basso, Catherine Blanpied, Claire Gaveriaux-Ruff, Nicolas Cenac, Gilles Dietrich
Summary: This study identifies the important role of the delta opioid receptor (DOR) in relieving intestinal inflammatory pain and suggests the potential of developing peripherally restricted DOR analgesics for intestinal disorders, which could avoid the side effects associated with drugs targeting the mu opioid receptor (MOR).
JOURNAL OF NEUROINFLAMMATION
(2022)
Review
Neurosciences
Paola Pacifico, James S. Coy-Dibley, Richard J. Miller, Daniela M. Menichella
Summary: This article reviews new approaches for treating peripheral neuropathic pain, including disease modifying therapies and advanced techniques for uncovering novel mechanisms. It also highlights the potential of drug treatment applied topically and the role of non-neuronal cells and communication between the skin and sensory afferents. Lastly, it discusses the current challenges in developing new therapies and improving the translation of research findings from animal models to the clinic.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Review
Pharmacology & Pharmacy
Magdalena Kocot-Kepska, Renata Zajaczkowska, Joanna Mika, David J. Kopsky, Jerzy Wordliczek, Jan Dobrogowski, Anna Przeklasa-Muszynska
Summary: Neuropathic pain in humans results from injuries or diseases of the somatosensory nervous system, and despite advancements in pain management, topical treatments are gaining popularity for their safety and targeted mechanisms. Active compounds in topical treatments exert multiple mechanisms of action on neuronal and non-neuronal cells, contributing to pain relief, but the specific impact in humans remains unclear. Evidence from clinical studies supports certain topical treatments as effective options for managing neuropathic pain.
Article
Neurosciences
Shivani Vaidya, P. A. Shantanu, Vinod Tiwari
Summary: The study demonstrated that DALDA exhibits a strong analgesic effect in vivo and possesses inhibitory effects on oxidative-inflammatory stress. By binding to multiple potential inflammatory targets, DALDA shows potential as a therapeutic for neuropathic pain.
NEUROSCIENCE LETTERS
(2021)
Article
Pharmacology & Pharmacy
Asmaa H. Nasser, Abdallah M. Gendy, Mohammed F. El-Yamany, Dalia M. El-Tanbouly
Summary: This study investigated the mechanism of neuropathic pain alleviation after paclitaxel administration. It was found that trimetazidine (TMZ) promotes the activation of extracellular signal-regulated kinases (ERK1/2) and upregulates neuronal progranulin (PGRN) and Notch1 receptors. This leads to the preservation of myelinated nerve fibers, alleviation of thermal, cold, and mechanical hyperalgesia/allodynia, and an anti-inflammatory effect.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Siavash Shahbazi Nia, Mohammad Anwar Hossain, Guangchen Ji, Sravan K. Jonnalagadda, Samuel Obeng, Md Ashrafur Rahman, Ali Ehsan Sifat, Saeideh Nozohouri, Collin Blackwell, Dhavalkumar Patel, Jon Thompson, Scott Runyon, Takato Hiranita, Christopher R. McCurdy, Lance McMahon, Thomas J. Abbruscato, Paul C. Trippier, Volker Neugebauer, Nadezhda A. German
Summary: Based on the structure of gliotoxin, two chemotypes with selective affinity to the kappa opioid receptor (KOR) were synthesized. Through medicinal chemistry and structure-activity relationship (SAR) studies, the required structural features for high affinity were identified, and advanced molecules with favorable properties were prepared. Compound 2 was shown to block the pain-relieving effect of a KOR agonist both in vitro and in vivo, indicating its potential application as a pain therapeutic.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biology
Martina Vincenzi, Michele Stanislaw Milella, Ginevra D'Ottavio, Daniele Caprioli, Ingrid Reverte, Daniela Maftei
Summary: Neuropathic pain originates from somatosensory nervous system injury or disease, and there are currently no satisfactory treatments. Upregulation of chemokines may be a common mechanism driving neuropathic pain, as well as consequences related to chronic opioid use.
Review
Biochemistry & Molecular Biology
Miao-Miao Tian, Yu-Xiang Li, Shan Liu, Chun-Hao Zhu, Xiao-Bing Lan, Juan Du, Lin Ma, Jia-Mei Yang, Ping Zheng, Jian-Qiang Yu, Ning Liu
Summary: Neuropathic pain is a burdensome disease with limited effectiveness and adverse reactions to current pharmacotherapy. Glycosides from natural compounds have shown potential as analgesics by regulating oxidative stress, transcriptional regulation, ion channels, and other mechanisms to alleviate neuropathic pain.
Article
Cell Biology
Qiansen Zhang, Yimin Ren, Yiqing Mo, Peipei Guo, Ping Liao, Yuncheng Luo, Jie Mu, Zhuo Chen, Yang Zhang, Ya Li, Linghui Yang, Daqing Liao, Jie Fu, Juwen Shen, Wei Huang, Xuewen Xu, Yanyan Guo, Lianghe Mei, Yunxia Zuo, Jin Liu, Huaiyu Yang, Ruotian Jiang
Summary: This study discovered the expression of neuronal Hv1 in peripheral sensory neurons and found that its up-regulation is associated with aggravated inflammation and nociception. Inhibiting neuronal Hv1 can reduce inflammatory pain and morphine-induced hyperalgesia and tolerance.
Article
Anesthesiology
Didier Bouhassira, Serge Perrot, Thibault Riant, Gaelle Martine-Fabre, Gisele Pickering, Caroline Maindet, Nadine Attal, Stephanie Ranque Garnier, Jean-Paul Nguyen, Emmanuelle Kuhn, Eric Viel, Patrick Kieffert, Thomas Toelle, Claire Delorme, Rodrigue Deleens, Patrick Ginies, Virginie Corand-Dousset, Clemence Dal-Col, Alain Serrie, Emmanuel Chevrillon, Christian Gov, Juan Fernando Ramirez-Gil, Cecile Delval, Manuella Schaller, Baptiste Bessiere, Patrick Houeto, Claudia Sommer
Summary: Nitrous oxide (N2O) is commonly used for anesthesia and short-duration analgesia. Research suggests that N2O/O-2 50%-50% mixture can induce long-lasting analgesic effects. A study on chronic peripheral neuropathic pain patients showed that a 1-hour administration of EMONO significantly improved evoked pain intensity and overall impression of change, with effects lasting up to 4 weeks after treatment.
Review
Biochemistry & Molecular Biology
Lin Li, Jing Chen, Yun-Qing Li
Summary: Neuropathic pain (NP) is a type of pain caused by damage or malfunction of the peripheral or central nervous system. It affects the physical and mental health of 7-10% of the general population. This literature review focuses on the role of downregulation of opioid receptors in the development of NP, particularly from the perspective of dorsal root ganglion, spinal cord, and supraspinal regions. The review also discusses the reasons for the poor efficacy of opioids in NP treatment, including opioid tolerance caused by NP and repeated opioid treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Correction
Multidisciplinary Sciences
Giovanna Del Vecchio, Dominika Labuz, Julia Temp, Viola Seitz, Michael Kloner, Roger Negrete, Antonio Rodriguez-Gaztelumendi, Marcus Weber, Halina Machelska, Christoph Stein
SCIENTIFIC REPORTS
(2020)
Review
Immunology
Halina Machelska, Melih Oe Celik
FRONTIERS IN IMMUNOLOGY
(2020)
Article
Pharmacology & Pharmacy
Luca Eibach, Simone Scheffel, Madeleine Cardebring, Marie Lettau, M. Ozgur Celik, Andreas Morguet, Robert Roehle, Christoph Stein
Summary: The study investigated the effectiveness of cannabidivarin (CBDV) for treating HIV-associated neuropathic pain and found that it did not significantly reduce pain intensity. The results suggest that CBDV has no impact on the amount of pain medication used, pain characteristics, or quality of life.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Chemistry, Medicinal
Samo Lesnik, Milan Hodoscek, Urban Bren, Christoph Stein, Ana-Nicoleta Bondar
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2020)
Article
Anesthesiology
Nicolas Massaly, Julia Temp, Halina Machelska, Christoph Stein
Review
Health Care Sciences & Services
Christoph Stein
CURRENT OPINION IN SUPPORTIVE AND PALLIATIVE CARE
(2020)
Article
Neurosciences
Dominika Labuz, Melih O. Celik, Viola Seitz, Halina Machelska
Summary: Interleukin-4 (IL-4) is an anti-inflammatory cytokine that can alleviate pain by releasing opioid peptides from infiltrating macrophages at injured nerves. This newly discovered mechanism involves PKA-mediated, PI3K-mediated, ryanodine receptor-mediated, and intracellular Ca21-mediated release from M1 macrophages of opioid peptides, which activate peripheral opioid receptors in injured tissue. Targeting the IL-4-opioid system in peripheral damaged tissue may offer a potential therapeutic approach with fewer central and systemic side effects.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Gastroenterology & Hepatology
Nestor Nivardo Jimenez-Vargas, Yang Yu, Dane D. Jensen, Diana Daeun Bok, Matthew Wisdom, Rocco Latorre, Cintya Lopez, Josue O. Jaramillo-Polanco, Claudius Degro, Mabel Guzman-Rodriguez, Quentin Tsang, Zachary Snow, Brian L. Schmidt, David E. Reed, Alan Edward Lomax, Kara Gross Margolis, Christoph Stein, Nigel W. Bunnett, Stephen J. Vanner
Summary: The fentanyl analogue NFEPP demonstrated effectiveness in inhibiting pain response in mice with colitis in an acidic environment, without causing respiratory depression, constipation, or hyperactivity. In contrast, fentanyl inhibited pain responses in both groups of mice and had side effects such as respiratory depression and hyperactivity.
Article
Multidisciplinary Sciences
Melih Oe Celik, Roger Negrete, Riccardo Di Rosso, Halina Machelska, Christoph Stein
Summary: Opioid agonist NFEPP can activate peripheral opioid receptors in injured tissue under acidic conditions, reducing side effects. By studying its interaction with the commonly used NSAID diclofenac, we found that diclofenac reduced inflammation-induced nociceptive responses and tissue acidosis, and had a moderate effect on the antinociceptive efficacy of NFEPP.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Arne Thies, Vikram Sunkara, Sourav Ray, Hanna Wulkow, M. Oezguer Celik, Fatih Yergoez, Christof Schuette, Christoph Stein, Marcus Weber, Stefanie Winkelmann
Summary: We have successfully designed, synthesized, and tested the prototype opioid painkiller NFEPP, which does not have adverse side effects. The design process was based on mathematical modeling of interactions between G-protein coupled receptors (GPCRs) and ligands, considering the different functions of GPCRs under pathological and healthy conditions. Additionally, we have proposed a novel stochastic model of GPCR function that takes into account intracellular dissociation of G-protein subunits and modulation of plasma membrane calcium channels, which depend on the parameters of inflamed and healthy tissue (pH, radicals). The model has been validated using in vitro experimental data for NFEPP and fentanyl at different pH values and radical concentrations.
SCIENTIFIC REPORTS
(2023)
Article
Anesthesiology
Claudius E. Degro, Nestor Nivardo Jimenez-Vargas, Quentin Tsang, Yang Yu, Mabel Guzman-Rodriguez, Elahe Alizadeh, David Hurlbut, David E. Reed, Alan E. Lomax, Christoph Stein, Nigel W. Bunnett, Stephen J. Vanner
Summary: This study found that repeated dosing of N-(3-fluoro-1-phenethylpiperidine-4-yl)-N-phenyl propionamide can provide safe and effective analgesia for colitis by targeting the acidified layers of the inflamed colon. The drug is able to inhibit human colonic nociceptors and has minimal side effects.
Article
Multidisciplinary Sciences
Ana Baamonde, Luis Menendez, Sara Gonzalez-Rodriguez, Ana Lastra, Viola Seitz, Christoph Stein, Halina Machelska
SCIENTIFIC REPORTS
(2020)