{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T13:06:59Z","timestamp":1789132019745,"version":"build-2803163510"},"reference-count":102,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>Human understanding of the nature of pain has undergone a profound shift from mechanical reductionism to a multidimensional, integrative approach. Among the many types of chronic pain, neuropathic pain (NP) has long been a key focus of research in the fields of neurobiology and pain medicine, owing to its high prevalence and complex mechanisms. Its core pathological feature is an abnormal increase in neuron excitability caused by peripheral and central sensitization. As the most important excitatory neurotransmitter in the nervous system, glutamate plays an irreplaceable and central role in signal transduction at every level of the pain transmission pathway. Therefore, investigating the mechanisms of analgesic effects mediated by glutamate and its receptors is of great significance for understanding the pathophysiological nature of NP. This paper focuses on the mechanisms of peripheral and central sensitisation mediated by glutamate and its receptors, exploring their potential effects as key analgesic targets in NP, with a view to providing a theoretical foundation and directions for clinical translation in research into the analgesic mechanisms of NP.<\/jats:p>","DOI":"10.3389\/fnagi.2026.1951251","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T12:17:46Z","timestamp":1789129066000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The excitatory neurotransmitter glutamate and its receptors: the culprits behind neuropathic pain?"],"prefix":"10.3389","volume":"18","author":[{"given":"Pengfei","family":"Qi","sequence":"first","affiliation":[{"name":"Heilongjiang University of Chinese Medicine","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongren","family":"Sun","sequence":"additional","affiliation":[{"name":"Heilongjiang University of Chinese Medicine","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongna","family":"Yin","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2356","DOI":"10.3390\/ijms26052356","article-title":"Molecular anatomy of synaptic and extrasynaptic neurotransmission between nociceptive primary afferents and spinal dorsal horn neurons","volume":"26","author":"Antal","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"S22","DOI":"10.1097\/j.pain.0000000000003064","article-title":"Beyond the study of pain: the evolving role of the International Association for the Study of Pain in global advocacy","volume":"164","author":"Arendt Nielsen","year":"2023","journal-title":"Pain"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1401","DOI":"10.1007\/s10571-022-01248-x","article-title":"Amygdala metabotropic glutamate receptor 1 influences synaptic transmission to participate in fentanyl-induced hyperalgesia in rats","volume":"43","author":"Bai","year":"2023","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1111\/j.1471-4159.2006.03913.x","article-title":"The glutamate\/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer","volume":"98","author":"Bak","year":"2006","journal-title":"J. Neurochem."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1146\/annurev-pharmtox-010818-021524","article-title":"Neuropathic pain: mechanism-based therapeutics","volume":"60","author":"Bannister","year":"2020","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"477","DOI":"10.2174\/1570159x11311050002","article-title":"Role of presynaptic glutamate receptors in pain transmission at the spinal cord level","volume":"11","author":"Bardoni","year":"2013","journal-title":"Curr. Neuropharmacol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/j.cell.2009.09.028","article-title":"Cellular and molecular mechanisms of pain","volume":"139","author":"Basbaum","year":"2009","journal-title":"Cell"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s10194-018-0885-8","article-title":"Increased thalamic glutamate\/glutamine levels in migraineurs","volume":"19","author":"Bathel","year":"2018","journal-title":"J. Headache Pain"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"789","DOI":"10.3390\/brainsci13050789","article-title":"IL-10\/\u03b2-endorphin-mediated neuroimmune modulation on microglia during antinociception","volume":"13","author":"Belo","year":"2023","journal-title":"Brain Sci."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1080\/14728222.2017.1328057","article-title":"Targeting dorsal root ganglia and primary sensory neurons for the treatment of chronic pain","volume":"21","author":"Berta","year":"2017","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1080\/14728222.2023.2247563","article-title":"Targeting dorsal root ganglia and primary sensory neurons for the treatment of chronic pain: an update","volume":"27","author":"Berta","year":"2023","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"4027","DOI":"10.3390\/cells11244027","article-title":"Pharmacological profile of MP-101, a novel non-racemic mixture of R- and S-dimiracetam with increased potency in rat models of cognition, depression and neuropathic pain","volume":"11","author":"Bonifacino","year":"2022","journal-title":"Cells"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/s0899-9007(01)00795-x","article-title":"Glutamine: an anaplerotic precursor","volume":"18","author":"Bowtell","year":"2002","journal-title":"Nutrition"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.neuron.2006.09.021","article-title":"Mechanisms of neuropathic pain","volume":"52","author":"Campbell","year":"2006","journal-title":"Neuron"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1038\/s41392-024-01845-w","article-title":"Pathology of pain and its implications for therapeutic interventions","volume":"9","author":"Cao","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"2307","DOI":"10.1016\/j.celrep.2018.02.021","article-title":"The \u03b12\u03b4-1-NMDA receptor complex is critically involved in neuropathic pain development and gabapentin therapeutic actions","volume":"22","author":"Chen","year":"2018","journal-title":"Cell Rep."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"e70327","DOI":"10.1111\/cns.70327","article-title":"Electroacupuncture regulates sympathetic nerve through the NTS(Glu)-RVLM circuit to relieve spontaneous pain in SNI rats","volume":"31","author":"Chen","year":"2025","journal-title":"CNS Neurosci. Ther."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"2082","DOI":"10.1016\/s0140-6736(21)00393-7","article-title":"Chronic pain: an update on burden, best practices, and new advances","volume":"397","author":"Cohen","year":"2021","journal-title":"Lancet"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.neuint.2016.05.009","article-title":"Neuronal vs glial glutamate uptake: resolving the conundrum","volume":"98","author":"Danbolt","year":"2016","journal-title":"Neurochem. Int."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1097\/aln.0000000000002648","article-title":"\u03b12\u03b4-1-bound N-methyl-D-aspartate receptors mediate morphine-induced hyperalgesia and analgesic tolerance by potentiating glutamatergic input in rodents","volume":"130","author":"Deng","year":"","journal-title":"Anesthesiology"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1889","DOI":"10.1007\/s00018-019-03047-y","article-title":"Presynaptic NMDA receptors control nociceptive transmission at the spinal cord level in neuropathic pain","volume":"76","author":"Deng","year":"","journal-title":"Cell. Mol. Life Sci."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1007\/s43440-024-00657-7","article-title":"mGlu4R, mGlu7R, and mGlu8R allosteric modulation for treating acute and chronic neurodegenerative disorders","volume":"76","author":"Domin","year":"2024","journal-title":"Pharmacol. Rep."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1016\/j.tins.2020.07.008","article-title":"How Do Sensory Neurons Sense Danger Signals?","volume":"43","author":"Donnelly","year":"2020","journal-title":"Trends Neurosci."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1089\/neu.2015.4373","article-title":"Glutamate neurotransmission in rodent models of traumatic brain injury","volume":"34","author":"Dorsett","year":"2017","journal-title":"J. Neurotrauma"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.1200\/jco.2013.51.7219","article-title":"Pain and nociception: mechanisms of cancer-induced bone pain","volume":"32","author":"Falk","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/0166-4328(95)00045-3","article-title":"Physiological release of excitatory amino acids","volume":"71","author":"Fillenz","year":"1995","journal-title":"Behav. Brain Res."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1265\/ehpm.24-00035","article-title":"Gabapentin improves neuropathic pain in Minamata disease model rats","volume":"29","author":"Fujimura","year":"2024","journal-title":"Environ. Health Prev. Med."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"109763","DOI":"10.1016\/j.neuropharm.2023.109763","article-title":"Optogenetic inhibition of spinal inhibitory neurons facilitates mechanical responses of spinal wide dynamic range neurons and causes mechanical hypersensitivity","volume":"242","author":"Fujiwara","year":"2024","journal-title":"Neuropharmacology"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"e95491","DOI":"10.1371\/journal.pone.0095491","article-title":"Increased response to glutamate in small diameter dorsal root ganglion neurons after sciatic nerve injury","volume":"9","author":"Gong","year":"2014","journal-title":"PLoS One"},{"key":"ref30","first-page":"S7","article-title":"Anatomy and physiology of glutamate in the CNS","volume":"44","author":"Greenamyre","year":"1994","journal-title":"Neurology"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1523\/jneurosci.1968-21.2021","article-title":"Theta-burst stimulation of primary afferents drives long-term potentiation in the spinal cord and persistent pain via \u03b12\u03b4-1-bound NMDA receptors","volume":"42","author":"Huang","year":"2022","journal-title":"J. Neurosci."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"e1943232023","DOI":"10.1523\/jneurosci.1943-23.2023","article-title":"Constitutive KCC2 cell- and synapse-specifically regulates NMDA receptor activity in the spinal cord","volume":"44","author":"Huang","year":"2024","journal-title":"J. Neurosci."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"7225","DOI":"10.1038\/s41467-025-62565-5","article-title":"SERBP1-PCIF1 complex-controlled m6Am modification in glutamatergic neurons of the primary somatosensory cortex is required for neuropathic pain in mice","volume":"16","author":"Huang","year":"2025","journal-title":"Nat. Commun."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"2422","DOI":"10.1016\/j.pain.2012.08.011","article-title":"Peripheral nerve injury produces a sustained shift in the balance between glutamate release and uptake in the dorsal horn of the spinal cord","volume":"153","author":"Inquimbert","year":"2012","journal-title":"Pain"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1007\/s12017-025-08848-y","article-title":"CaMKII\u03b1-NpHR-mediated optogenetic inhibition of DRG glutamatergic neurons by flexible optic Fiber alleviates chronic neuropathic pain","volume":"27","author":"Islam","year":"","journal-title":"NeuroMolecular Med."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s10194-025-01977-6","article-title":"Optogenetic inhibition of ventrolateral orbitofrontal cortex astrocytes facilitates ventrolateral periaqueductal gray glutamatergic activity to reduce hypersensitivity in infraorbital nerve injury rat model","volume":"26","author":"Islam","year":"","journal-title":"J. Headache Pain"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"e2509315122","DOI":"10.1073\/pnas.2509315122","article-title":"Lipid raft proteomics identify endothelial myosin-9 (MYH9) as a regulator of low-density lipoprotein transcytosis and atherosclerosis","volume":"122","author":"Jang","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1038\/s42003-025-08772-8","article-title":"Isolation, characterization and testing of RNA aptamers targeting glutamate receptors in a rat spinal cord injury pain model","volume":"8","author":"Jergova","year":"2025","journal-title":"Commun. Biol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.neuroscience.2025.11.031","article-title":"Electroacupuncture alleviates chemotherapy-induced peripheral neuropathy and anxiety by reducing TRPC6\/PKC-dependent activation of glutamatergic neurons in the paraventricular thalamic nucleus","volume":"592","author":"Jiang","year":"2026","journal-title":"Neuroscience"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"e076036","DOI":"10.1136\/bmj-2023-076036","article-title":"Chronic pain: definitions and diagnosis","volume":"381","author":"Kang","year":"2023","journal-title":"BMJ"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"107605","DOI":"10.1016\/j.celrep.2020.107605","article-title":"Defining the Homo- and Heterodimerization propensities of metabotropic glutamate receptors","volume":"31","author":"Lee","year":"2020","journal-title":"Cell Rep."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1016\/j.cell.2016.02.027","article-title":"Communication in neural circuits: tools, opportunities, and challenges","volume":"164","author":"Lerner","year":"2016","journal-title":"Cell"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"108275","DOI":"10.1016\/j.pharmthera.2022.108275","article-title":"Targeting mGluR2\/3 for treatment of neurodegenerative and neuropsychiatric diseases","volume":"239","author":"Li","year":"2022","journal-title":"Pharmacol. Ther."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"109396","DOI":"10.1016\/j.celrep.2021.109396","article-title":"\u03b12\u03b4-1 switches the phenotype of synaptic AMPA receptors by physically disrupting heteromeric subunit assembly","volume":"36","author":"Li","year":"2021","journal-title":"Cell Rep."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"e20699","DOI":"10.7717\/peerj.20699","article-title":"Exercise alleviates allodynia and hyperalgesia concomitant with improvements in aberrant primary afferents and spinal circuit inhibition in the dorsal horn of rats with incomplete spinal cord injury","volume":"14","author":"Li","year":"2026","journal-title":"PeerJ"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"3727","DOI":"10.1111\/jnc.15800","article-title":"Astrocytic purinergic signalling contributes to the development and maintenance of neuropathic pain via modulation of glutamate release","volume":"168","author":"Liu","year":"2024","journal-title":"J. Neurochem."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"2529","DOI":"10.1097\/j.pain.0000000000003647","article-title":"A glutamatergic brain neural circuit is critical for modulating trigeminal neuropathic pain","volume":"166","author":"Liu","year":"2025","journal-title":"Pain"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"21057","DOI":"10.1038\/s41598-025-01501-5","article-title":"Downregulation of EAAT-2 impairs chronic neuropathic pain via increasing of plasma glutamate after herpes zoster infection","volume":"15","author":"Lu","year":"2025","journal-title":"Sci. Rep."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.freeradbiomed.2019.06.002","article-title":"Upregulating Nrf2 in the RVLM ameliorates sympatho-excitation in mice with chronic heart failure","volume":"141","author":"Ma","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1111\/cns.13694","article-title":"Spinal microglial \u03b2-endorphin signaling mediates IL-10 and exenatide-induced inhibition of synaptic plasticity in neuropathic pain","volume":"27","author":"Ma","year":"2021","journal-title":"CNS Neurosci. Ther."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/nrn725","article-title":"The structure and function of glutamate receptor ion channels","volume":"3","author":"Madden","year":"2002","journal-title":"Nat. Rev. Neurosci."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1007\/s00018-018-3002-x","article-title":"The dual face of glutamate: from a neurotoxin to a potential survival factor-metabolic implications in health and disease","volume":"76","author":"Magi","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1016\/j.tips.2012.08.001","article-title":"Current challenges in translational pain research","volume":"33","author":"Mao","year":"2012","journal-title":"Trends Pharmacol. Sci."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1002\/jnr.23561","article-title":"Maintaining the presynaptic glutamate supply for excitatory neurotransmission","volume":"93","author":"Marx","year":"2015","journal-title":"J. Neurosci. Res."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1146\/annurev.physiol.66.050802.084104","article-title":"Structure and function of glutamate receptor ion channels","volume":"66","author":"Mayer","year":"2004","journal-title":"Annu. Rev. Physiol."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"2608","DOI":"10.3390\/cells11162608","article-title":"Recent advances in the modulation of pain by the metabotropic glutamate receptors","volume":"11","author":"Mazzitelli","year":"2022","journal-title":"Cells"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"108801","DOI":"10.1016\/j.neuropharm.2021.108801","article-title":"The evidence for and consequences of metabotropic glutamate receptor heterodimerization","volume":"199","author":"McCullock","year":"2021","journal-title":"Neuropharmacology"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.3390\/ijms20051030","article-title":"The reactive plasticity of hippocampal ionotropic glutamate receptors in animal epilepsies","volume":"20","author":"Mih\u00e1ly","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"3729","DOI":"10.1523\/jneurosci.3212-17.2018","article-title":"Regulation of nociceptive glutamatergic signaling by presynaptic Kv3.4 channels in the rat spinal dorsal horn","volume":"38","author":"Muqeem","year":"2018","journal-title":"J. Neurosci."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"e157","DOI":"10.1097\/j.pain.0000000000002755","article-title":"Descending projections from the insular cortex to the trigeminal spinal subnucleus caudalis facilitate excitatory outputs to the parabrachial nucleus in rats","volume":"164","author":"Nakaya","year":"2023","journal-title":"Pain"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1007\/s10571-017-0489-x","article-title":"The orally active noncompetitive AMPAR antagonist Perampanel attenuates focal cerebral ischemia injury in rats","volume":"38","author":"Niu","year":"2018","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.neuint.2014.11.006","article-title":"Glutamate: where does it come from and where does it go?","volume":"88","author":"Olsen","year":"2015","journal-title":"Neurochem. Int."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1177\/1073858402238515","article-title":"GABA and glutamate in the human brain","volume":"8","author":"Petroff","year":"2002","journal-title":"Neuroscientist"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/j.pbb.2007.10.006","article-title":"Evidence for the involvement of glutamatergic and GABAergic systems and protein kinase a pathway in the antinociceptive effect caused by p-methoxy-diphenyl diselenide in mice","volume":"88","author":"Pinto","year":"2008","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.pharmthera.2013.12.012","article-title":"Metabotropic glutamatergic receptors and their ligands in drug addiction","volume":"142","author":"Pomierny-Chamio\u0142o","year":"2014","journal-title":"Pharmacol. Ther."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"11111","DOI":"10.3390\/ijms252011111","article-title":"Exploring the therapeutic potential of N-methyl-D-aspartate receptor antagonists in neuropathic pain management","volume":"25","author":"Pu\u0219ca\u0219u","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"2874","DOI":"10.1038\/s41598-025-86885-0","article-title":"NaHS modulates astrocytic EAAT2 expression to impact SNI-induced neuropathic pain and depressive-like behaviors","volume":"15","author":"Qi","year":"2025","journal-title":"Sci. Rep."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"1976","DOI":"10.1097\/j.pain.0000000000001939","article-title":"The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises","volume":"161","author":"Raja","year":"2020","journal-title":"Pain"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"1681","DOI":"10.3390\/biom11111681","article-title":"The \u03c31 receptor and the HINT1 protein control \u03b12\u03b41 binding to glutamate NMDA receptors: implications in neuropathic pain","volume":"11","author":"Rodr\u00edguez-Mu\u00f1oz","year":"2021","journal-title":"Biomolecules"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1016\/j.neuroscience.2017.06.049","article-title":"A tale of two circuits: CCK(NTS) neuron stimulation controls appetite and induces opposing motivational states by projections to distinct brain regions","volume":"358","author":"Roman","year":"2017","journal-title":"Neuroscience"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1111\/bph.16296","article-title":"Intravenous recombinant cerebellin 1 treatment restores signalling by spinal glutamate delta 1 receptors and mitigates chronic pain","volume":"181","author":"Sabnis","year":"2024","journal-title":"Br. J. Pharmacol."},{"key":"ref72","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1152\/physrev.00025.2008","article-title":"Models and mechanisms of hyperalgesia and allodynia","volume":"89","author":"Sandk\u00fchler","year":"2009","journal-title":"Physiol. Rev."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"929","DOI":"10.2174\/156802606777323719","article-title":"Glial modulation of GABAergic and glutamat ergic neurotransmission","volume":"6","author":"Schousboe","year":"2006","journal-title":"Curr. Top. Med. Chem."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1038\/s42003-025-07733-5","article-title":"mGluR5-mediated astrocytes hyperactivity in the anterior cingulate cortex contributes to neuropathic pain in male mice","volume":"8","author":"Shen","year":"2025","journal-title":"Commun. Biol."},{"key":"ref75","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1177\/10738584211021018","article-title":"Group 1 metabotropic glutamate receptors in neurological and psychiatric diseases: mechanisms and prospective","volume":"28","author":"Su","year":"2022","journal-title":"Neuroscientist"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"5974","DOI":"10.1038\/s41467-020-19767-w","article-title":"Parabrachial nucleus circuit governs neuropathic pain-like behavior","volume":"11","author":"Sun","year":"2020","journal-title":"Nat. Commun."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/s0168-0102(96)01131-5","article-title":"Distribution and projection of the medullary cardiovascular control neurons containing glutamate, glutamic acid decarboxylase, tyrosine hydroxylase and phenylethanolamine N-methyltransferase in rats","volume":"27","author":"Suzuki","year":"1997","journal-title":"Neurosci. Res."},{"key":"ref78","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1038\/s42003-025-07874-7","article-title":"A glutamatergic innervation from medial area of secondary visual cortex to lateral posterior thalamic nucleus facilitates nociceptive and neuropathic pain","volume":"8","author":"Tan","year":"2025","journal-title":"Commun. Biol."},{"key":"ref79","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1016\/s0753-3322(02)00285-8","article-title":"Glutamine and glutamate","volume":"56","author":"Tapiero","year":"2002","journal-title":"Biomed. Pharmacother."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"106492","DOI":"10.1016\/j.phrs.2022.106492","article-title":"Glutamatergic systems in neuropathic pain and emerging non-opioid therapies","volume":"185","author":"Temmermand","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref81","doi-asserted-by":"publisher","first-page":"2023","DOI":"10.1016\/s0140-6736(21)01194-6","article-title":"Rethinking chronic pain","volume":"397","year":"2021","journal-title":"Lancet"},{"key":"ref82","doi-asserted-by":"publisher","first-page":"105786","DOI":"10.1016\/j.neuint.2024.105786","article-title":"Red nucleus mGluR1 and mGluR5 facilitate the development of neuropathic pain through stimulating the expressions of TNF-\u03b1 and IL-1\u03b2","volume":"178","author":"Tian","year":"2024","journal-title":"Neurochem. Int."},{"key":"ref83","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1038\/jcbfm.2013.114","article-title":"Glutamatergic and GABAergic TCA cycle and neurotransmitter cycling fluxes in different regions of mouse brain","volume":"33","author":"Tiwari","year":"2013","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref84","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1038\/nrn2947","article-title":"Neuronal circuitry for pain processing in the dorsal horn","volume":"11","author":"Todd","year":"2010","journal-title":"Nat. Rev. Neurosci."},{"key":"ref85","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1097\/j.pain.0000000000000160","article-title":"A classification of chronic pain for ICD-11","volume":"156","author":"Treede","year":"2015","journal-title":"Pain"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1124\/jpet.123.001669","article-title":"Mechanism of analgesia by Gabapentinoid drugs: involvement of modulation of synaptogenesis and trafficking of glutamate-gated ion channels","volume":"388","author":"Varadi","year":"2024","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref87","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.neuint.2005.04.012","article-title":"Role of glutamine and neuronal glutamate uptake in glutamate homeostasis and synthesis during vesicular release in cultured glutamatergic neurons","volume":"47","author":"Waagepetersen","year":"2005","journal-title":"Neurochem. Int."},{"key":"ref88","doi-asserted-by":"publisher","first-page":"101786","DOI":"10.1016\/j.xcrm.2024.101786","article-title":"Clinical pain management: current practice and recent innovations in research","volume":"5","author":"Wang","year":"2024","journal-title":"Cell Rep. Med."},{"key":"ref89","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s40659-020-00303-5","article-title":"Altered thalamic neurotransmitters metabolism and functional connectivity during the development of chronic constriction injury induced neuropathic pain","volume":"53","author":"Wang","year":"2020","journal-title":"Biol. Res."},{"key":"ref90","doi-asserted-by":"publisher","first-page":"5124","DOI":"10.1038\/s41467-023-40860-3","article-title":"A glutamatergic DRN-VTA pathway modulates neuropathic pain and comorbid anhedonia-like behavior in mice","volume":"14","author":"Wang","year":"2023","journal-title":"Nat. Commun."},{"key":"ref91","doi-asserted-by":"publisher","first-page":"S100","DOI":"10.1038\/sj.bjp.0706444","article-title":"The glutamate story","volume":"147","author":"Watkins","year":"2006","journal-title":"Br. J. Pharmacol."},{"key":"ref92","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.tins.2004.04.005","article-title":"Structure and gating of the glutamate receptor ion channel","volume":"27","author":"Wollmuth","year":"2004","journal-title":"Trends Neurosci."},{"key":"ref93","doi-asserted-by":"publisher","first-page":"11701","DOI":"10.1523\/jneurosci.1799-17.2017","article-title":"Autocrine Interleukin-10 mediates glucagon-like Peptide-1 receptor-induced spinal microglial \u03b2-endorphin expression","volume":"37","author":"Wu","year":"2017","journal-title":"J. Neurosci."},{"key":"ref94","doi-asserted-by":"publisher","first-page":"108539","DOI":"10.1016\/j.pharmthera.2023.108539","article-title":"Presynaptic glutamate receptors in nociception","volume":"251","author":"Xie","year":"2023","journal-title":"Pharmacol. Ther."},{"key":"ref95","doi-asserted-by":"publisher","first-page":"7445","DOI":"10.1523\/jneurosci.1812-08.2008","article-title":"Presynaptic and postsynaptic amplifications of neuropathic pain in the anterior cingulate cortex","volume":"28","author":"Xu","year":"2008","journal-title":"J. Neurosci."},{"key":"ref96","doi-asserted-by":"publisher","first-page":"109641","DOI":"10.1016\/j.neuropharm.2023.109641","article-title":"Understanding the initiation, delivery and processing of bone cancer pain from the peripheral to the central nervous system","volume":"237","author":"Yang","year":"2023","journal-title":"Neuropharmacology"},{"key":"ref97","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1007\/s12264-023-01126-6","article-title":"Peripheral mechanism of Cancer-induced bone pain","volume":"40","author":"Yang","year":"2024","journal-title":"Neurosci. Bull."},{"key":"ref98","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1093\/jnen\/nlad056","article-title":"Caveolin-1 is essential for the increased release of glutamate in the anterior cingulate cortex in neuropathic pain mice","volume":"82","author":"Yang","year":"2023","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref99","doi-asserted-by":"publisher","first-page":"109936","DOI":"10.1016\/j.celrep.2021.109936","article-title":"Activation of parabrachial nucleus - ventral tegmental area pathway underlies the comorbid depression in chronic neuropathic pain in mice","volume":"37","author":"Zhang","year":"2021","journal-title":"Cell Rep."},{"key":"ref100","doi-asserted-by":"publisher","first-page":"107869","DOI":"10.1016\/j.neuropharm.2019.107869","article-title":"Wnt1\/\u03b2-catenin signaling upregulates spinal VGLUT2 expression to control neuropathic pain in mice","volume":"164","author":"Zhang","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref101","doi-asserted-by":"publisher","first-page":"441","DOI":"10.2147\/jpr.S446803","article-title":"Understanding of spinal wide dynamic range neurons and their modulation on pathological pain","volume":"17","author":"Zhang","year":"2024","journal-title":"J. Pain Res."},{"key":"ref102","doi-asserted-by":"publisher","first-page":"ENEURO.0454","DOI":"10.1523\/eneuro.0454-23.2024","article-title":"Modulation of comorbid chronic neuropathic pain and anxiety-like behaviors by glutamatergic neurons in the ventrolateral periaqueductal gray and the analgesic and anxiolytic effects of electroacupuncture","volume":"11","author":"Zhu","year":"2024","journal-title":"eNeuro"}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2026.1951251\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T12:17:47Z","timestamp":1789129067000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2026.1951251\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,11]]},"references-count":102,"alternative-id":["10.3389\/fnagi.2026.1951251"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2026.1951251","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,11]]},"article-number":"1951251"}}