Review
Pharmacology & Pharmacy
Sara Marsango, Graeme Milligan
Summary: GPR84 is a little-studied receptor that belongs to the rhodopsin-like class A G protein-coupled receptors, but it has attracted attention for its therapeutic potential. Its expression is up-regulated in response to acute inflammation and in inflammatory diseases, and activation of the receptor is involved in regulating pro-inflammatory responses and cell migration of the innate immune system. While GPR84 primarily signals through G(alpha i/o)-proteins, there is evidence that it can also recruit arrestin proteins upon agonist activation, which affects receptor internalization and desensitization. However, the phosphorylation patterns of GPR84 and their role in these processes are not well understood.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Endocrinology & Metabolism
Siyuan Shen, Chang Zhao, Chao Wu, Suyue Sun, Ziyan Li, Wei Yan, Zhenhua Shao
Summary: GPCRs, as the largest family of transmembrane proteins, regulate various physiological processes. However, their complicated signal transduction pathways and difficulties in drug development have presented challenges. By identifying new ligands that bind to allosteric sites, safer drugs for treating various diseases can be designed.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Alexander O. Shpakov
Summary: Allosteric regulation plays a critical role in the functioning of GPCRs and their signaling pathways. The complexity of allosteric effects caused by various regulators determines the multiplicity and topology of allosteric sites in GPCRs. These sites are involved in the regulation of receptor activity, GPCR-complex formation, and endocytosis. They are also targets for synthetic allosteric regulators and modulators. The review provides an overview of the principles and mechanisms of GPCRs allosteric regulation, the diversity of allosteric sites, and the endogenous and synthetic allosteric regulators.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Simona Daniele, Simona Saporiti, Stefano Capaldi, Deborah Pietrobono, Lara Russo, Uliano Guerrini, Tommaso Laurenzi, Elham Ataie Kachoie, Luca Palazzolo, Vincenzo Russo, Maria Pia Abbracchio, Ivano Eberini, Maria Letizia Trincavelli
Summary: GPR17, a key regulator of myelination, is activated by endogenous ligands and pro-inflammatory molecules. This study investigates the structural and functional interactions between GPR17 and chemokine receptors CXCR2 and CXCR4. The results show that these receptors can form heterodimers and modulate intracellular cAMP levels. This cross-talk between receptors could impact the neuroinflammatory environment associated with demyelinating events.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Pedro Renault, Jesus Giraldo
Summary: Computational tools have been used to estimate the druggability of allosteric sites in GPCRs, but predicting hydrophobic sites remains challenging. This study introduces a dynamics-based approach using experimental structures, normal mode analysis, and molecular dynamics simulations to identify allosteric sites in beta 2AR, GCGR, and M2 receptors, showing promising predictive value.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Louise Dickson, Martin Teall, Elodie Chevalier, Toni Cheung, Gemma M. Liwicki, Stephen Mack, Anne Stephenson, Kathryn White, Richard Fosbeary, David C. Harrison, Nicola L. Brice, Kevin Doyle, Roberto Ciccocioppo, Chaobo Wu, Sarah Almond, Toshal R. Patel, Philip Mitchell, Matt Barnes, Andrew P. Ayscough, Lee A. Dawson, Mark Carlton, Roland W. Burli
Summary: In this study, highly potent and selective mGluR7 agonists, including CVN636, were identified, optimized, and characterized. CVN636 demonstrated CNS penetrance and efficacy in an in vivo rodent model of alcohol use disorder, suggesting its potential as a drug candidate in CNS disorders involving mGluR7 and glutamatergic dysfunction.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Medicinal
Louise Dickson, Martin Teall, Elodie Chevalier, Toni Cheung, Gemma M. Liwicki, Stephen Mack, Anne Stephenson, Kathryn White, Richard Fosbeary, David C. Harrison, Nicola L. Brice, Kevin Doyle, Roberto Ciccocioppo, Chaobo Wu, Sarah Almond, Toshal R. Patel, Philip Mitchell, Matt Barnes, Andrew P. Ayscough, Lee A. Dawson, Mark Carlton, Roland W. Burli
Summary: In this study, highly potent and selective agonists for the low affinity metabotropic glutamate receptor mGluR7 were identified, optimized, and characterized. The chromane CVN636, in particular, showed exceptional selectivity for mGluR7 and demonstrated CNS penetrance and efficacy in an in vivo rodent model of alcohol use disorder. As such, CVN636 has the potential to be a drug candidate for CNS disorders involving mGluR7 and glutamatergic dysfunction.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Neurosciences
Prachi Ojha, Subhajit Pal, Samarjit Bhattacharyya
Summary: Norbin protein plays a critical role in the internalization process of Group I mGluRs and may be associated with mGluR-mediated synaptic plasticity.
JOURNAL OF NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Raudah Lazim, Donghyuk Suh, Jai Woo Lee, Thi Ngoc Lan Vu, Sanghee Yoon, Sun Choi
Summary: The presence of GPCR dimers has sparked research into their importance in disease pathogenesis and drug design, uncovering new signaling pathways and potential therapeutic targets. The increasing influence of computational methods in research is providing new avenues for understanding the functions and interactions of GPCRs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Amanda E. Wakefield, David Bajusz, Dima Kozakov, Gyoergy M. Keseru, Sandor Vajda
Summary: Despite the limited number of GPCR structures cocrystallized with allosteric inhibitors, protein mapping has revealed the presence of druggable sites at the same locations in a large variety of GPCRs. These sites cluster at nine distinct locations and can be specifically targeted for allosteric modulation across GPCRs. The FTMap server facilitates protein mapping and is freely available for academic and governmental use.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Review
Pharmacology & Pharmacy
Xiao Tang, Yaolin Hou, Thue W. Schwartz, Jesper Z. Haeggstrom
Summary: Eicosanoids, derived from arachidonic acid, are bioactive compounds that play crucial roles in physiology and disease, particularly in inflammatory conditions of multiple organ systems. Recent research has shown that G-protein coupled receptors can sense extracellular metabolites and regulate inflammatory responses, including eicosanoid production.
BIOCHEMICAL PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Xiaoqing Guo, Qin Li, Shulan Pi, Yuanpeng Xia, Ling Mao
Summary: P2Y receptors are a critical group of G protein-coupled receptors that signal through dimers, playing diverse roles in physiology and pathology. Research has shown the significance of dimerization between P2Y receptors and other receptors in cardiovascular and cerebrovascular processes.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Vanessa Pereira, Juri Aparicio Arias, Amadeu Llebaria, Cyril Goudet
Summary: Neuropathic pain is a challenging condition to manage. In this study, the role of the amygdala in regulating neuropathic pain was investigated. The activation of mGlu4 receptors in the amygdala was found to alleviate sensory and depressive-like symptoms in a mouse model of neuropathy.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Stephen P. H. Alexander, Arthur Christopoulos, Anthony P. Davenport, Eamonn Kelly, Alistair Mathie, John A. Peters, Emma L. Veale, Jane F. Armstrong, Elena Faccenda, Simon D. Harding, Adam J. Pawson, Christopher Southan, Jamie A. Davies, Maria Pia Abbracchio, Wayne Alexander, Khaled Al-hosaini, Magnus Baeck, Nicholas M. Barnes, Ross Bathgate, Jean-Martin Beaulieu, Kenneth E. Bernstein, Bernhard Bettler, Nigel J. M. Birdsall, Victoria Blaho, Francois Boulay, Corinne Bousquet, Hans Braeuner-Osborne, Geoffrey Burnstock, Girolamo Calo, Justo P. Castano, KevinJ Catt, Stefania Ceruti, Paul Chazot, Nan Chiang, Bice Chini, Jerold Chun, Antonia Cianciulli, Olivier Civelli, Lucie H. Clapp, Rejean Couture, Zsolt Csaba, Claes Dahlgren, Gordon Dent, Khuraijam Dhanachandra Singh, Steven D. Douglas, Pascal Dournaud, Satoru Eguchi, Emanuel Escher, Edward J. Filardo, Tung Fong, Marta Fumagalli, Raul R. Gainetdinov, Marc de Gasparo, Craig Gerard, Marvin Gershengorn, Fernand Gobeil, Theodore L. Goodfriend, Cyril Goudet, Karen J. Gregory, Andrew L. Gundlach, Joerg Hamann, Julien Hanson, Richard L. Hauger, Debbie L. Hay, Akos Heinemann, Morley D. Hollenberg, Nicholas D. Holliday, Mastgugu Horiuchi, Daniel Hoyer, Laszlo Hunyady, Ahsan Husain, Adriaan P. IJzerman, Tadashi Inagami, Kenneth A. Jacobson, Robert T. Jensen, Ralf Jockers, Deepa Jonnalagadda, Sadashiva Karnik, Klemens Kaupmann, Jacqueline Kemp, Charles Kennedy, Yasuyuki Kihara, Takio Kitazawa, Pawel Kozielewicz, Hans-Juergen Kreienkamp, Jyrki P. Kukkonen, Tobias Langenhan, Katie Leach, Davide Lecca, John D. Lee, Susan E. Leeman, Jerome Leprince, Xaria X. Li, Tom Lloyd Williams, Stephen J. Lolait, Amelie Lupp, Robyn Macrae, Janet Maguire, Jean Mazella, Craig A. McArdle, Shlomo Melmed, Martin C. Michel, Laurence J. Miller, Vincenzo Mitolo, Bernard Mouillac, Christa E. Mueller, Philip Murphy, Jean-Louis Nahon, Tony Ngo, Xavier Norel, Duuamene Nyimanu, Anne-Marie Ocarroll, Stefan Offermanns, Maria Antonietta Panaro, Marc Parmentier, Roger G. Pertwee, Jean-Philippe Pin, Eric R. Prossnitz, Mark Quinn, Rithwik Ramachandran, Manisha Ray, Rainer K. Reinscheid, Philippe Rondard, G. Enrico Rovati, Chiara Ruzza, Gareth J. Sanger, Torsten Schoeneberg, Gunnar Schulte, Stefan Schulz, Deborah L. Segaloff, Charles N. Serhan, Leigh A. Stoddart, Yukihiko Sugimoto, Roger Summers, Valerie P. Tan, David Thal, Walter (Wally) Thomas, PieterB M. W. M. Timmermans, Kalyan Tirupula, Giovanni Tulipano, Hamiyet Unal, Thomas Unger, Celine Valant, Patrick Vanderheyden, David Vaudry, Hubert Vaudry, Jean-Pierre Vilardaga, Christopher S. Walker, Ji Ming Wang, Donald T. Ward, Hans-Juergen Wester, Gary B. Willars, Trent M. Woodruff, Chengcan Yao, Richard D. Ye
Summary: The Concise Guide to PHARMACOLOGY 2021/22 presents concise overviews of nearly 1900 human drug targets with an emphasis on selective pharmacology, along with links to a more detailed knowledgebase. It serves as a permanent, citable record for researchers, providing useful information in the field of pharmacology.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Cell Biology
Jakob Mitgau, Julius Franke, Camilla Schinner, Gabriele Stephan, Sandra Berndt, Dimitris G. Placantonakis, Hermann Kalwa, Volker Spindler, Caroline Wilde, Ines Liebscher
Summary: This study provides information on the structural requirements and forces needed for ECM-mediated activation of the GPR126 receptor. The N terminus of GPR126 acts as an allosteric module that can fine-tune receptor activation in a context-specific manner.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Neurosciences
L. Trovo, C. Fuchs, R. De Rosa, I. Barbiero, M. Tramarin, E. Ciani, L. Rusconi, C. Kilstrup-Nielsen
NEUROBIOLOGY OF DISEASE
(2020)
Article
Biochemical Research Methods
Ting Huang, Meena Choi, Manuel Tzouros, Sabrina Golling, Nikhil Janak Pandya, Balazs Banfai, Tom Dunkley, Olga Vitek
MOLECULAR & CELLULAR PROTEOMICS
(2020)
Article
Multidisciplinary Sciences
Filip Roudnicky, Jitao David Zhang, Bo Kyoung Kim, Nikhil J. Pandya, Yanjun Lan, Lisa Sach-Peltason, Heloise Ragelle, Pamela Strassburger, Sabine Gruener, Mirjana Lazendic, Sabine Uhles, Franco Revelant, Oliv Eidam, Gregor Sturm, Verena Kueppers, Klaus Christensen, Leonard D. Goldstein, Manuel Tzouros, Balazs Banfai, Zora Modrusan, Martin Graf, Christoph Patsch, Mark Burcin, Claas A. Meyer, Peter D. Westenskow, Chad A. Cowan
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Biochemical Research Methods
Meena Choi, Jeremy Carver, Cristina Chiva, Manuel Tzouros, Ting Huang, Tsung-Heng Tsai, Benjamin Pullman, Oliver M. Bernhardt, Ruth Huttenhain, Guo Ci Teo, Yasset Perez-Riverol, Jan Muntel, Maik Mueller, Sandra Goetze, Maria Pavlou, Erik Verschueren, Bernd Wollscheid, Alexey I. Nesvizhskii, Lukas Reiter, Tom Dunkley, Eduard Sabido, Nuno Bandeira, Olga Vitek
Article
Neurosciences
Alessandra Porcu, Rafaela Mostallino, Valeria Serra, Miriam Melis, Valeria Sogos, Sarah Beggiato, Luca Ferraro, Fabrizio Manetti, Beatrice Gianibbi, Bernhard Bettler, Federico Corelli, Claudia Mugnaini, M. Paola Castelli
Summary: This study characterized the negative allosteric modulator COR758 for GABA(B) receptors, showing its potential as a therapeutic candidate by inhibiting G protein signaling. COR758 may serve as a scaffold for developing additional NAMs for therapeutic intervention by interacting with an allosteric binding site of GABA(B) receptors.
Article
Multidisciplinary Sciences
Li-Pao Fang, Na Zhao, Laura C. Caudal, Hsin-Fang Chang, Renping Zhao, Ching-Hsin Lin, Nadine Hainz, Carola Meier, Bernhard Bettler, Wenhui Huang, Anja Scheller, Frank Kirchhoff, Xianshu Bai
Summary: Early disruption of GABA/TNFSF12 signaling between interneurons and oligodendrocyte precursor cells impairs prefrontal cortical network activity and social cognitive behavior later in life. The study identifies a bidirectional communication pathway between fast spiking interneurons and oligodendrocyte precursor cells that determines the density and function of interneurons in the developing prefrontal cortex. Interruption of this signaling results in reduced myelination, hypoactivity of interneurons, changes in cortical network activities, and impaired social cognitive behavior. Glial transmitter receptors play a crucial role in fine-tuning distinct brain functions.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Maria Lucia Cediel, Michal Stawarski, Xavier Blanc, Lenka Noskova, Martin Magner, Konrad Platzer, Janina Gburek-Augustat, Dustin Baldridge, John N. Constantino, Emmanuelle Ranza, Bernhard Bettler, Stylianos E. Antonarakis
Summary: GABA(B) receptors are responsible for neuronal inhibition in the central nervous system. Variants in GABBR2 have been associated with certain phenotypes, while no phenotypes have been established for GABBR1 variants. This study identified four GABBR1 variants in individuals with motor and/or language delay, and functional characterization revealed their impact on GABA potency and efficacy, providing insights into disease severity and potential therapeutic strategies.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Endocrinology & Metabolism
Noelia P. Di Giorgio, Marianne Bizzozzero-Hiriart, Pablo N. Surkin, Esteban Repetto, Maria M. Bonaventura, Florencia N. Tabares, Nadia S. Bourguignon, Ayelen Converti, Juan M. Riano Gomez, Bernhard Bettler, Victoria Lux-Lantos
Summary: GABA and Kisspeptin play critical roles in reproduction and metabolic control. A unique mouse lacking GABAB receptors in Kiss1 cells showed severe impairment in glucose homeostasis, which worsened with aging. These results reinforce the involvement of Kisspeptin in metabolic regulation and highlight the importance of GABA through GABAB receptors in the regulation of the peripheral pancreas Kisspeptin system.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Biochemistry & Molecular Biology
Steven F. Baker, Helene Meistermann, Manuel Tzouros, Aaron Baker, Sabrina Golling, Juliane Siebourg Polster, Mitchell P. Ledwith, Anthony Gitter, Angelique Augustin, Hassan Javanbakht, Andrew Mehle
Summary: The host range of influenza virus is limited by successful interactions between the virus and cellular proteins. The study identifies a cellular protein called cMECR that interacts with the viral polymerase and suppresses viral replication by blocking assembly of viral ribonucleoprotein complexes.
Article
Biology
Pascal Dominic Rem, Vita Sereikaite, Diego Fernandez-Fernandez, Sebastian Reinartz, Daniel Ulrich, Thorsten Fritzius, Luca Trovo, Salome Roux, Ziyang Chen, Philippe Rondard, Jean-Philippe Pin, Jochen Schwenk, Bernd Fakler, Martin Gassmann, Tania Rinaldi Barkat, Kristian Stromgaard, Bernhard Bettler
Summary: Amyloid-beta precursor protein (APP) regulates neuronal activity through the release of secreted APP (sAPP) acting at cell surface receptors. A 17 amino acid peptide (APP17) derived from APP binds to the extracellular sushi domain 1 (SD1) of GABA(B) receptors (GBRs). However, APP17 does not influence GBR activity in heterologous cells, indicating that sAPP exerts its neuronal effects through receptors other than GBRs.
Article
Cell Biology
Nikhil J. Pandya, Congwei Wang, Veronica Costa, Paul Lopatta, Sonja Meier, F. Isabella Zampeta, A. Mattijs Punt, Edwin Mientjes, Philip Grossen, Tania Distler, Manuel Tzouros, Yasmina Marti, Balazs Banfai, Christoph Patsch, Soren Rasmussen, Marius Hoener, Marco Berrera, Thomas Kremer, Tom Dunkley, Martin Ebeling, Ben Distel, Ype Elgersma, Ravi Jagasia
Summary: Angelman syndrome is a neurodevelopmental disorder caused by the loss of maternal UBE3A, and studying neurons derived from patients with AS and neurotypical individuals have revealed the potential involvement of the protein PEG10 in AS pathophysiology. Further research on PEG10 and its interaction with RNA and certain proteins may shed light on the mechanisms underlying this disorder.
CELL REPORTS MEDICINE
(2021)
Correction
Neurosciences
Lucia Privitera, Ellen L. Hogg, Matthias Gaestel, Mark J. Wall, Sonia A. L. Correa
Article
Neurosciences
Li-Ya Jiang, Guan-Hao Wang, Jing-Jiao Xu, Xiao-Li Li, Xiao-Yan Lin, Xiang Fang, Hong-Xu Zhang, Mei Feng, Chun-Ming Jiang
Summary: This study reveals the importance of LINC00473 in regulating temozolomide (TMZ) resistance in glioblastoma (GB) and its potential mechanism. By regulating the expression of CEBP alpha and MGMT, LINC00473 promotes the formation of chemoresistance. Furthermore, LINC00473 can transfer chemoresistance to adjacent sensitive cells through exosomes.
Article
Neurosciences
Olga Kopach, Tetyana Pivneva, Nataliya Fedirko, Nana Voitenko
Summary: This study found that diabetic animals exhibit severe xerostomia characterized by reduced saliva flow rate, diminished total protein content, and decreased amylase activity. The impaired saliva production in diabetes is associated with reduced and delayed intracellular Ca2+ signals in submandibular acinar cells, caused by malfunctioning mitochondria. Targeting malfunctioning mitochondria may be a potential strategy for the treatment of diabetic xerostomia.
Article
Neurosciences
Nicholas M. Timme, Cherish E. Ardinger, Seth D. C. Weir, Rachel Zelaya-Escobar, Rachel Kruger, Christopher C. Lapish
Summary: This study aimed to assess aversion-resistant drinking behavior in head-fixed mice and explore the relationship between non-consummatory behaviors and aversion-resistant drinking. The results showed that head-fixed mice exhibited heterogenous levels of aversion-resistant drinking and non-consummatory behaviors were related to the intensity of this behavior.
Article
Neurosciences
David R. Maguire, Charles P. France
Summary: Methocinnamox (MCAM) is a novel, long-acting opioid receptor antagonist that effectively decreases fentanyl self-administration and prevents opioid overdose in monkeys. The study demonstrates the potential therapeutic utility of MCAM in the treatment of opioid use disorder.
Article
Neurosciences
Xiang Li, Dan Feng, Shenglu Ma, Mingxing Li, Shulei Zhao, Man Tang
Summary: This study investigated the effects of fluoxetine on neurochemical, neurobiological, and neurobehavioral changes in different subregions of the hippocampus. The results showed that fluoxetine increased dialysate 5-HT, decreased membrane 5-HTT protein, and increased cytoplasmic fraction. Additionally, fluoxetine reduced immobility times in behavioral tests, with greater effects observed in the ventral subregion compared to the dorsal subregion.
Article
Neurosciences
Alexander V. Zholos, Mariia I. Melnyk, Dariia O. Dryn
Summary: Acetylcholine is an important neurotransmitter in visceral smooth muscles, activating M2 and M3 muscarinic receptors to cause smooth muscle excitation and contraction. This review focuses on the cellular and molecular mechanisms underlying acetylcholine-induced depolarisation and smooth muscle contraction, as well as the effects of anticholinergic drugs on gastrointestinal motility. The knowledge gained from recent studies has greatly expanded our understanding of these processes.
Article
Neurosciences
Zhenlong Li, Hsien-Yu Peng, Chau-Shoun Lee, Tzer-Bin Lin, Ming-Chun Hsieh, Cheng-Yuan Lai, Han-Fang Wu, Lih-Chyang Chen, Mei-Ci Chen, Dylan Chou
Summary: Methylone shows significant efficacy in treating depression and social deficits, making it an ideal candidate for anti-depressant medication.
Article
Neurosciences
Aline Freyssin, Allison Carles, Sarra Guehairia, Gilles Rubinstenn, Tangui Maurice
Summary: This study explores the potential of combining FENM and S1R agonists in the treatment of Alzheimer's disease. The results showed that most FENM-based combinations can protect against learning deficits caused by A beta 25-35, with better efficacy in short-term memory.
Article
Neurosciences
J. D. Lorente, J. Cuitavi, L. Rullo, S. Candeletti, P. Romualdi, L. Hipolito
Summary: This study analyzed the effects of pain on negative affect in different sexes and time courses, as well as the involvement of the dynorphinergic and corticotropin releasing factor systems in these pain-related behaviors. The results showed sex and time-dependent anxiety- and anhedonia-like behaviors induced by pain in female rats. The recruitment of KOR/DYN in the NAc was identified as a key neurological substrate mediating pain-induced behavioral alterations.
Article
Neurosciences
Rongjun Liu, Daofan Sun, Xiuzhong Xing, Qingge Chen, Bo Lu, Bo Meng, Hui Yuan, Lan Mo, Liufang Sheng, Jinwei Zheng, Qiusheng Wang, Junping Chen, Xiaowei Chen
Summary: The coexistence of pain and depression is frequently observed in patients with chronic pain and depression. Oxytocin, a neuropeptide, has been reported to relieve chronic pain and depressive symptoms. This study investigated the effect of intranasal oxytocin on neuropathic pain and comorbid depressive symptoms, and found that oxytocin attenuated depression-like behavior but did not alleviate mechanical hyperalgesia. The results suggest that intranasal oxytocin may have the potential to treat depressive symptoms in neuropathic pain patients.