Article
Clinical Neurology
Xiaoman Yuan, Siyi Han, Fengtian Zhao, Anne Manyande, Feng Gao, Jie Wang, Wen Zhang, Xuebi Tian
Summary: This study developed a new minimally invasive and intuitive intraganglionic injection technique in mice, which showed positive results. Moreover, this method serves as a valuable resource for planning preclinical studies of DRG injection.
FRONTIERS IN NEUROLOGY
(2023)
Article
Pharmacology & Pharmacy
Christopher Katnik, Javier Cuevas
Summary: The study focuses on intracellular ionic imbalance resulting from ischemic stroke, and the impact of NKCC1 antagonists on Na+ and Ca2+ overload. Loop diuretics BMN and EA inhibited ischemia-acidosis induced Ca2+ overload, but did not reduce Na+ increases.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Haoyi Yang, Zhiming Shan, Weijie Guo, Yuwei Wang, Shuxian Cai, Fuyi Li, Qiaojie Huang, Jessica Aijia Liu, Chi Wai Cheung, Song Cai
Summary: Neuropathic pain is a global chronic disease with limited treatment options. This study identifies Narirutin, a natural compound derived from Citrus unshiu, as a potential analgesic for neuropathic pain. The research suggests that Na(v)1.7, a subtype of voltage-gated sodium channels, may be the molecular target for Narirutin's antinociceptive effects. This finding provides insights for the development of novel and selective analgesic drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Anesthesiology
Theodora Kalpachidou, Philipp Malsch, Yanmei Qi, Norbert Mair, Stephan Geley, Serena Quarta, Kai K. Kummer, Michaela Kress
Summary: Peripheral nerve injuries can lead to neuropathic pain, and the TRPA1 ion channel is a potential target for analgesic therapies. In this study, we found a regulatory link between IL-6/gp130 and TRPA1 in a mouse model of nerve injury, providing a solution to the enigma of TRPA1 regulation after injury.
Article
Pharmacology & Pharmacy
Paz Duran, Santiago Loya-Lopez, Dongzhi Ran, Cheng Tang, Aida Calderon-Rivera, Kimberly Gomez, Harrison J. Stratton, Sun Huang, Ya-ming Xu, E. M. Kithsiri Wijeratne, Samantha Perez-Miller, Zhiming Shan, Song Cai, Anna T. Gabrielsen, Angie Dorame, Kyleigh A. Masterson, Omar Alsbiei, Cynthia L. Madura, Guoqin Luo, Aubin Moutal, John Streicher, Gerald W. Zamponi, A. A. Leslie Gunatilaka, Rajesh Khanna
Summary: This study identified argentatin C, a compound derived from the Native American medicinal plant Parthenium incanum, which can block the activity of voltage-gated sodium and calcium channels and has potential as a novel treatment for painful conditions. Experimental results demonstrated that argentatin C decreased ion currents and excitability in sensory neurons and relieved postsurgical pain in a mouse model. Therefore, argentatin C may serve as an alternative therapy for chronic pain management.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Neurosciences
Vanessa Pereira, Sylvain Lamoine, Melissa Cumenal, Stephane Lolignier, Youssef Aissouni, Anne Pizzoccaro, Laetitia Prival, David Balayssac, Alain Eschalier, Emmanuel Bourinet, Jerome Busserolles
Summary: Peripheral neuropathy induced by oxaliplatin is characterized by acute pain symptoms, primarily caused by ion channel expression modulations in dorsal root ganglia neurons. The downregulation of K+ channels, including TREK and TRAAK, is identified as an important factor contributing to oxaliplatin-induced hypersensitivity. NRSF and HDACs play crucial roles in the dysregulation of K+ channels.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Biology
Shane J. F. Cronin, Lance S. Davidow, Anthony C. Arvanites, Lee L. Rubin, Josef M. Penninger, Clifford J. Woolf
Summary: Management of neuropathic pain is challenging due to limited effectiveness and potential side effects of current analgesics. This study presents a phenotypic screen to identify compounds that regulate the expression of the algesic gene Gch1, which is linked to neuropathic pain. By establishing a platform to monitor and target Gch1 expression in individual injured neurons, this approach provides valuable insights into the pathways and signals involved in regulating GCH1 and BH4 levels upon nerve injury.
Article
Biology
Shane J. F. Cronin, Lance S. Davidow, Anthony C. Arvanites, Lee L. Rubin, Josef M. Penninger, Clifford J. Woolf
Summary: The management of neuropathic pain is challenging, and there is a need to discover non-addictive and safe analgesics. This study describes a screening method to target the expression of the algesic gene Gch1 and identify compounds that regulate neuropathic pain. The approach provides valuable insights into the regulation of GCH1 and BH4 levels after nerve injury.
Article
Neurosciences
Anne Jacobi, Nicholas M. Tran, Wenjun Yan, Inbal Benhar, Feng Tian, Rebecca Schaffer, Zhigang He, Joshua R. Sanes
Summary: This study examined three interventions that enhance survival and regeneration of mouse retinal ganglion cells (RGCs) after optic nerve crush (ONC) injury. Manipulation of multiple pathways is required for type-independent axon regeneration. The analysis of gene expression using single-cell transcriptomics identified genes selectively expressed by RGCs likely to be dying, surviving, or regenerating. Overexpression of genes associated with the regeneration program improved both survival and axon regeneration, suggesting the potential of mechanistic analysis in identifying novel therapeutic strategies.
Article
Multidisciplinary Sciences
Antonia Colom-Casasnovas, Edith Garay, Abraham Cisneros-Mejorado, Manuel B. Aguilar, Fernando Lazcano-Perez, Rogelio O. Arellano, Judith Sanchez-Rodriguez
Summary: The venom from sea anemone Bartholomea annulata has potent effects on both Na+ channels and GABA(A) receptors in the central nervous system, inhibiting the neuronal action potential and activating GABA(A) receptors. This reveals novel effects on mammalian ion channels crucial for nervous system signaling.
SCIENTIFIC REPORTS
(2022)
Article
Pharmacology & Pharmacy
Ilaria Piccialli, Roselia Ciccone, Agnese Secondo, Francesca Boscia, Valentina Tedeschi, Valeria de Rosa, Pasquale Cepparulo, Lucio Annunziato, Anna Pannaccione
Summary: The activity of NCX, especially the NCX3 isoform, was found to be upregulated in AD neurons, contributing to an increase in ER Ca2+ content while not affecting cytosolic Ca2+ concentrations. Functional coupling between NCX3 and the voltage-gated Na(V)1.6 channels was uncovered, suggesting a potential role of NCX3 in the Ca2+ remodelling of AD neurons.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Nolan M. Dvorak, Cynthia M. Tapia, Aditya K. Singh, Timothy J. Baumgartner, Pingyuan Wang, Haiying Chen, Paul A. Wadsworth, Jia Zhou, Fernanda Laezza
Summary: Voltage-gated Na+ channels are crucial for action potentials, with isoforms like Na(v)1.1, Na(v)1.2, and Na(v)1.6 showing differential expression in the central nervous system. Targeting specific isoforms could lead to promising neuromodulators with potential therapeutic value.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Renfei Qi, Junping Cao, Yufang Sun, Yanping Li, Zitong Huang, Dongsheng Jiang, Xing-Hong Jiang, Terrance P. Snutch, Yuan Zhang, Jin Tao
Summary: In neuropathic pain, miR-32-5p plays a functional role by regulating Cav3.2 channels. Nerve injury-induced histone methylation decreases miR-32-5p expression, leading to increased Cav3.2 protein expression and pain-related behaviors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biology
Timothy J. Baumgartner, Zahra Haghighijoo, Nana A. Goode, Nolan M. Dvorak, Parsa Arman, Fernanda Laezza
Summary: Alzheimer's disease is characterized by two major histopathological abnormalities: extracellular plaques composed of amyloid beta and intracellular hyperphosphorylated tau. Attenuation of hippocampal hyperactivity, which is linked to dysfunction of voltage-gated Na+ channels, has emerged as a promising therapeutic strategy for early-stage AD. This review explores the role of Nav channels in neuronal function, their connections to AD pathology, and their potential as therapeutic targets.
Review
Neurosciences
Stephanie Bigsby, Joseph Neapetung, Veronica A. Campanucci
Summary: This review provides an updated report on the role of Na-V channels in pain pathologies, especially in diabetic sensory neuropathy (DSN). Current treatments fail to reverse or successfully manage DSN.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Immunology
Li Zhang, Wenrui Xie, Jingdong Zhang, Hailey Shanahan, Raquel Tonello, Sang Hoon Lee, Judith A. Strong, Temugin Berta, Jun -Ming Zhang
Summary: Chronic low back pain is a common condition with high societal costs and often ineffective treatments. This study found that the CCR2/CCL2 system plays a key role in establishing the pain state in this model of inflammatory low back pain and radiculopathy, with different subsets of macrophages potentially influencing the pain state.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
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
Immunology
M. Elizabeth Deerhake, Keiko Danzaki, Makoto Inoue, Emre D. Cardakli, Toshiaki Nonaka, Nupur Aggarwal, William E. Barclay, Ru-Rong Ji, Mari L. Shinohara
Summary: This study revealed that Dectin-1 limits experimental autoimmune encephalomyelitis (EAE) by inducing the gene expression of the neuroprotective molecule Osm through a Card9-independent pathway. The Osm receptor functions in astrocytes to reduce EAE severity. The study introduces a mechanism of beneficial myeloid cell-astrocyte crosstalk regulated by a Dectin-1 pathway.
Review
Multidisciplinary Sciences
Natasha C. Brigham, Ru-Rong Ji, Matthew L. Becker
Summary: The study reviews the use of polymeric materials in post-operative pain management devices and highlights opportunities for improvement in current systems. Pain management plays a significant role in patient comfort, care quality, and compliance.
NATURE COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Arjun Muralidharan, Alexander Samoshkin, Marino Convertino, Marjo Hannele Piltonen, Pavel Gris, Jian Wang, Changyu Jiang, Richard Klares, Alexander Linton, Ru-Rong Ji, William Maixner, Nikolay V. Dokholyan, Jeffrey S. Mogil, Luda Diatchenko
Summary: This study developed compounds selective for 6TM- or 7TM-mu receptors through virtual screening and experimental validation, demonstrating their potential analgesic effects and serving as valuable research tools for the development of novel analgesics.
BRITISH JOURNAL OF PHARMACOLOGY
(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
Multidisciplinary Sciences
Sangsu Bang, Christopher R. Donnelly, Xin Luo, Maria Toro-Moreno, Xueshu Tao, Zilong Wang, Sharat Chandra, Andrey V. Bortsov, Emily R. Derbyshire, Ru-Rong Ji
Summary: GPR37 was found to have a protective role in multiple infection and sepsis models, with mice lacking Gpr37 showing increased mortality following infection challenges. The drugs ARU and NPD1 could protect wild-type mice from sepsis, but this protection was lost in Gpr37-deficient mice.
NATURE COMMUNICATIONS
(2021)
Editorial Material
Neurosciences
Ru-Rong Ji
NEUROSCIENCE BULLETIN
(2022)
Article
Biochemistry & Molecular Biology
Elodie Ehret, Yannick Jaeger, Chloe Sergi, Anne-Marie Merillat, Thibaud Peyrollaz, Deepika Anand, Qing Wang, Frederique Ino, Marc Maillard, Stephan Kellenberger, Ivan Gautschi, Roman Szabo, Thomas H. Bugge, Lotte K. Vogel, Edith Hummler, Simona Frateschi
Summary: The proteolytic activity of CAP1/Prss8 is not necessary for activating ENaC, and the activation of ENaC can be maintained through alternative pathways when CAP1/Prss8 is absent.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yihan Liao, Yinshi Ren, Xin Luo, Anthony J. Mirando, Jason T. Long, Abigail Leinroth, Ru-Rong Ji, Matthew J. Hilton
Summary: This study reveals the role of interleukin-6 (IL-6) in regulating cartilage degradation and pain in posttraumatic osteoarthritis (PTOA). Genetic ablation of Il6 reduces cartilage catabolism, innervation of the knee joint, and nociceptive signaling in male mice with PTOA. However, it does not improve subchondral bone sclerosis or chondrocyte apoptosis. The study highlights IL-6 as a potential target for disease-modifying drugs for PTOA in a sex-specific manner.
Article
Anesthesiology
Kenta Furutani, Ouyang Chen, Aidan McGinnis, Yuqing Wang, Charles N. Serhan, Trond Vidar Hansen, Ru-Rong Ji
Summary: The article demonstrates that 3-oxa-PD1 effectively reduces both acute and chronic itch in mouse models by regulating synaptic transmission and astroglial LCN2 production. Stable SPM analogs like 3-oxa-PD1 could be useful in treating pruritus associated with different skin injuries.
Review
Cell Biology
Aidan McGinnis, Ru-Rong Ji
Summary: Preclinical studies have found that glial cells play a crucial role in the development and maintenance of neuropathic pain in conditions such as diabetes, chemotherapy, major surgeries, and virus infections. Satellite glial cells (SGCs) in the peripheral nervous system (PNS) and astrocytes in the central nervous system (CNS) exhibit similar characteristics and functions in the genesis of neuropathic pain. However, SGCs are not simply peripheral astrocytes and have unique roles and interactions. Recent findings also suggest that SGCs are enriched with proteins related to fatty acid metabolism, which may have implications for novel therapeutic approaches targeting glial cells.
Article
Immunology
Chunjing Bao, Ouyang Chen, Huaxin Sheng, Jeffrey Zhang, Yikai Luo, Byron W. Hayes, Han Liang, Wolfgang Liedtke, Ru-Rong Ji, Soman N. Abraham
Summary: IgE-mediated anaphylaxis is a life-threatening systemic reaction triggered by allergens, resulting in the release of mediators from mast cells. The drop in body temperature associated with anaphylaxis in mice also involves the activation of the body's thermoregulatory neural circuit. This circuit is activated by chymase from mast cells stimulating TRPV1+ sensory neurons, leading to hypothermia.
SCIENCE IMMUNOLOGY
(2023)
Article
Medicine, Research & Experimental
Ouyang Chen, Qianru He, Qingjian Han, Kenta Furutani, Yun Gu, Madelynne Olexa, Ru-Rong Ji
Summary: Our understanding of neuropathic itch is limited due to a lack of relevant animal models. In this study, we established a mouse model of chronic itch by inoculating cutaneous T cell lymphoma (CTCL) in mice. The model exhibited lymphoma growth, immune cell accumulation, and persistent pruritus. We observed time-dependent changes in nerve innervations and identified different mechanisms underlying acute, chronic, and neuropathic itch.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Review
Biochemistry & Molecular Biology
Qin Zhang, Sangsu Bang, Sharat Chandra, Ru-Rong Ji
Summary: Inflammation causes pain, but it has been found that acute inflammation can also resolve pain through specialized pro-resolving mediators (SPMs) and macrophage signaling. GPR37, expressed in neurons and oligodendrocytes, is involved in various disorders and has recently been identified as being expressed in macrophages. Activation of GPR37 enhances macrophage phagocytosis and promotes the resolution of inflammatory pain. Novel ligands of GPR37, such as neuroprotectin D1 (NPD1) and osteocalcin (OCN), have shown analgesic effects in animal models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
