{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:16:03Z","timestamp":1792167363177,"version":"4.4.0"},"reference-count":118,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T00:00:00Z","timestamp":1711065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The dorsal root ganglion (DRG) serves as a pivotal site for managing chronic pain through dorsal root ganglion stimulation (DRG-S). In recent years, the DRG-S has emerged as an attractive modality in the armamentarium of neuromodulation therapy due to its accessibility and efficacy in alleviating chronic pain refractory to conventional treatments. Despite its therapeutic advantages, the precise mechanisms underlying DRG-S-induced analgesia remain elusive, attributed in part to the diverse sensory neuron population within the DRG and its modulation of both peripheral and central sensory processing pathways. Emerging evidence suggests that DRG-S may alleviate pain by several mechanisms, including the reduction of nociceptive signals at the T-junction of sensory neurons, modulation of pain gating pathways within the dorsal horn, and regulation of neuronal excitability within the DRG itself. However, elucidating the full extent of DRG-S mechanisms necessitates further exploration, particularly regarding its supraspinal effects and its interactions with cognitive and affective networks. Understanding these mechanisms is crucial for optimizing neurostimulation technologies and improving clinical outcomes of DRG-S for chronic pain management. This review provides a comprehensive overview of the DRG anatomy, mechanisms of action of the DRG-S, and its significance in neuromodulation therapy for chronic pain.<\/jats:p>","DOI":"10.3390\/ijms25073591","type":"journal-article","created":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T10:03:59Z","timestamp":1711101839000},"page":"3591","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Mechanisms of Action of Dorsal Root Ganglion Stimulation"],"prefix":"10.3390","volume":"25","author":[{"given":"Alaa","family":"Abd-Elsayed","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53792, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swarnima","family":"Vardhan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale New Haven Health, Bridgeport Hospital, Bridgeport, CT 06605, USA"},{"name":"Advanced Spine on Park Avenue, New York, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5080-6390","authenticated-orcid":false,"given":"Abhinav","family":"Aggarwal","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale New Haven Health, Bridgeport Hospital, Bridgeport, CT 06605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhurima","family":"Vardhan","sequence":"additional","affiliation":[{"name":"Argonne Leadership Computing Facility, Argonne National Laboratory, Lemont, IL 60439, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudhir A.","family":"Diwan","sequence":"additional","affiliation":[{"name":"Advanced Spine on Park Avenue, New York, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Goldberg, D.S., and McGee, S. (2011). Pain as a Global Public Health Priority. BMC Public Health, 11.","DOI":"10.1186\/1471-2458-11-770"},{"key":"ref_2","unstructured":"Institute of Medicine (US) Committee on Advancing Pain Research, Care, and Education (2011). Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research, National Academies Press."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.jpain.2012.03.009","article-title":"The Economic Costs of Pain in the United States","volume":"13","author":"Gaskin","year":"2012","journal-title":"J. Pain"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"ES9","DOI":"10.36076\/ppj.2012\/15\/ES9","article-title":"Opioid epidemic in the United States","volume":"15","author":"Manchikanti","year":"2012","journal-title":"Pain Physician"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1213\/00000539-196705000-00009","article-title":"Electrical inhibition of pain: Experimental evaluation","volume":"46","author":"Shealy","year":"1967","journal-title":"Anesth. Analg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e113020","DOI":"10.5812\/aapm.113020","article-title":"Dorsal Root Ganglion (DRG) and Chronic Pain","volume":"11","author":"Berger","year":"2021","journal-title":"Anesthesiol. Pain Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/ner.12247","article-title":"The Dorsal Root Ganglion in Chronic Pain and as a Target for Neuromodulation: A Review","volume":"18","author":"Krames","year":"2015","journal-title":"Neuromodulation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1111\/ner.12651","article-title":"Relevant Anatomy, Morphology, and Implantation Techniques of the Dorsal Root Ganglia at the Lumbar Levels","volume":"20","author":"Vancamp","year":"2017","journal-title":"Neuromodulation"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1097\/j.pain.0000000000000814","article-title":"Dorsal Root Ganglion Stimulation Yielded Higher Treatment Success Rate for Complex Regional Pain Syndrome and Causalgia at 3 and 12 Months: A Randomized Comparative Trial","volume":"158","author":"Deer","year":"2016","journal-title":"Pain"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1111\/ner.12692","article-title":"DRG Spinal Cord Stimulation as Solution for Patients with Severe Pain Due to Anterior Cutaneous Nerve Entrapment Syndrome: A Case Series","volume":"21","author":"Mol","year":"2018","journal-title":"Neuromodulation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/ner.12013","article-title":"A prospective study of dorsal root ganglion stimulation for the relief of chronic pain","volume":"16","author":"Deer","year":"2013","journal-title":"Neuromodulation"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/ner.12798","article-title":"Evaluating Dorsal Root Ganglion Stimulation in a Prospective Dutch Cohort","volume":"22","author":"Huygen","year":"2019","journal-title":"Neuromodulation"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.1093\/pm\/pnz012","article-title":"Unique Characteristics of the Dorsal Root Ganglion as a Target for Neuromodulation","volume":"20","author":"Esposito","year":"2019","journal-title":"Pain Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1148\/radiology.178.3.1994428","article-title":"Lumbar Spinal Nerves in the Neural Foramen: MR Appearance","volume":"178","author":"Kostelic","year":"1991","journal-title":"Radiology"},{"key":"ref_15","unstructured":"Grandhi, R.K., and Abd-Elsayed, A. (2019). Textbook of Neuroanesthesia and Neurocritical Care, Springer."},{"key":"ref_16","unstructured":"Ahimsadasan, N., Reddy, V., Khan Suheb, M.Z., and Kumar, A. (2022). StatPearls, StatPearls Publishing."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.neulet.2018.04.003","article-title":"Participation of Satellite Glial Cells of the Dorsal Root Ganglia in Acute Nociception","volume":"676","author":"Lemes","year":"2018","journal-title":"Neurosci. Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1002\/cne.20713","article-title":"Phylogenetic Investigation of Dogiel\u2019s Pericellular Nests and Cajal\u2019s Initial Glomeruli in the Dorsal Root Ganglion","volume":"491","author":"Matsuda","year":"2005","journal-title":"J. Comp. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.pneurobio.2018.05.002","article-title":"The Intriguing Nature of Dorsal Root Ganglion Neurons: Linking Structure with Polarity and Function","volume":"168","author":"Nascimento","year":"2018","journal-title":"Prog. Neurobiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"939","DOI":"10.4103\/1673-5374.250566","article-title":"Gene Expression Changes in Dorsal Root Ganglia Following Peripheral Nerve Injury: Roles in Inflammation, Cell Death and Nociception","volume":"14","author":"Martin","year":"2019","journal-title":"Neural Regen. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1111\/joa.13544","article-title":"The Structure of Sensory Afferent Compartments in Health and Disease","volume":"241","author":"Middleton","year":"2021","journal-title":"J. Anat."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.1016\/S0304-3959(99)00135-9","article-title":"Unexplained Peculiarities of the Dorsal Root Ganglion","volume":"82","author":"Devor","year":"1999","journal-title":"Pain"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1227\/NEU.0b013e318241ace1","article-title":"Sensory Neurons of the Human Brachial Plexus","volume":"70","author":"West","year":"2012","journal-title":"Neurosurgery"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1002\/ca.20472","article-title":"Clinical Anatomy of the C1 Dorsal Root, Ganglion, and Ramus: A Review and Anatomical Study","volume":"20","author":"Tubbs","year":"2007","journal-title":"Clin. Anat."},{"key":"ref_25","first-page":"105","article-title":"Morphometric evaluation of the sacral dorsal root ganglia. A cadaveric study","volume":"20","author":"Ebraheim","year":"1998","journal-title":"Surg. Radiol. Anat."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.neuron.2014.01.018","article-title":"Transmitting pain and itch messages: A contemporary view of the spinal cord circuits that generate gate control","volume":"82","author":"Braz","year":"2014","journal-title":"Neuron"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"W26","DOI":"10.2214\/AJR.16.17471","article-title":"The Lumbar Neural Foramen and Transforaminal Epidural Steroid Injections: An Anatomic Review with Key Safety Considerations in Planning the Percutaneous Approach","volume":"209","author":"Mandell","year":"2017","journal-title":"Am. J. Roentgenol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"398","DOI":"10.4097\/kjae.2010.59.6.398","article-title":"Position of Dorsal Root Ganglia in the Lumbosacral Region in Patients with Radiculopathy","volume":"59","author":"Moon","year":"2010","journal-title":"Korean J. Anesthesiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.rbo.2014.07.011","article-title":"Anatomical Study on the Relationship between the Dorsal Root Ganglion and the Intervertebral Disc in the Lumbar Spine","volume":"50","author":"Vialle","year":"2015","journal-title":"Rev. Bras. Ortop."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"372","DOI":"10.36076\/ppj.2002\/5\/372","article-title":"Anatomy of the Intervertebral Foramen","volume":"4","author":"Gilchrist","year":"2002","journal-title":"Pain Physician"},{"key":"ref_31","first-page":"1744","article-title":"Vascularization of the Dorsal Root Ganglia and Peripheral Nerve of the Mouse: Implications for Chemical-Induced Peripheral Sensory Neuropathies","volume":"4","author":"Herrera","year":"2008","journal-title":"Mol. Pain"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1002\/(SICI)1097-0029(19961001)35:2<122::AID-JEMT3>3.0.CO;2-S","article-title":"Vascular permeability in the peripheral autonomic and somatic nervous systems: Controversial aspects and comparisons with the blood-brain barrier","volume":"35","author":"Kiernan","year":"1996","journal-title":"Microsc. Res. Tech."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/359647a0","article-title":"A Functional Barrier to Movement of Lipids in Polarized Neurons","volume":"359","author":"Kobayashi","year":"1992","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1113\/jphysiol.1991.sp018419","article-title":"Protons Activate a Cation Conductance in a Sub-population of Rat Dorsal Root Ganglion Neurones","volume":"433","author":"Bevan","year":"1991","journal-title":"J. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1152\/jn.1990.64.6.1733","article-title":"Cross-Excitation in Dorsal Root Ganglia of Nerve-Injured and Intact Rats","volume":"64","author":"Devor","year":"1990","journal-title":"J. Neurophysiol."},{"key":"ref_36","unstructured":"Kim, D.H., and Imran, M.A. (2009). Leland Stanford Junior University and Spinal Modulation LLC. Method and System for Stimulating a Dorsal Root Ganglion. (7,580,753), U.S. Patent."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/cns.13192","article-title":"Mechanism of Dorsal Root Ganglion Stimulation for Pain Relief in Painful Diabetic Polyneuropathy Is Not Dependent on GABA Release in the Dorsal Horn of the Spinal Cord","volume":"26","author":"Koetsier","year":"2019","journal-title":"CNS Neurosci. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1111\/ner.13398","article-title":"Conventional Dorsal Root Ganglion Stimulation in an Experimental Model of Painful Diabetic Peripheral Neuropathy: A Quantitative Immunocytochemical Analysis of Intracellular \u0393-Aminobutyric Acid in Dorsal Root Ganglion Neurons","volume":"24","author":"Franken","year":"2021","journal-title":"Neuromodul. Technol. Neural Interface"},{"key":"ref_39","first-page":"951","article-title":"MR assessment of the normal position of the spinal cord in the spinal canal","volume":"15","author":"Holsheimer","year":"1994","journal-title":"Am. J. Neuroradiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/mrm.21260","article-title":"Investigation of human cervical and upper thoracic spinal cord motion: Implications for imaging spinal cord structure and function","volume":"58","author":"Figley","year":"2007","journal-title":"Magn. Reson. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/ner.12217","article-title":"Lack of body positional effects on paresthesias when stimulating the dorsal root ganglion (DRG) in the treatment of chronic pain","volume":"18","author":"Kramer","year":"2015","journal-title":"Neuromodulation"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1111\/j.1525-1403.2009.00269.x","article-title":"Patient perspectives on the efficacy and ergonomics of rechargeable spinal cord stimulators","volume":"13","author":"Lam","year":"2010","journal-title":"Neuromodulation"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0304-3959(99)00259-6","article-title":"Do beliefs, coping, and catastrophizing independently predict functioning in patients with chronic pain?","volume":"85","author":"Turner","year":"2000","journal-title":"Pain"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1007\/s00701-022-05161-6","article-title":"Frequency dependency of therapeutic efficacy in dorsal root ganglion stimulation for neuropathic pain","volume":"164","author":"Piedade","year":"2022","journal-title":"Acta Neurochir."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1111\/ner.13323","article-title":"Mechanisms for the Clinical Utility of Low-Frequency Stimulation in Neuromodulation of the Dorsal Root Ganglion","volume":"24","author":"Chapman","year":"2021","journal-title":"Neuromodulation"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1111\/ner.13322","article-title":"Very Low Frequencies Maintain Pain Relief from Dorsal Root Ganglion Stimulation: An Evaluation of Dorsal Root Ganglion Neurostimulation Frequency Tapering","volume":"24","author":"Chapman","year":"2021","journal-title":"Neuromodulation"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1007\/s00701-023-05500-1","article-title":"Effect of low-frequency dorsal root ganglion stimulation in the treatment of chronic pain","volume":"165","author":"Piedade","year":"2023","journal-title":"Acta Neurochir."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1016\/j.neurom.2022.04.050","article-title":"Dorsal Root Ganglion Stimulation as a Salvage Therapy Following Failed Spinal Cord Stimulation","volume":"25","author":"Chapman","year":"2022","journal-title":"Neuromodulation"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1080\/14737175.2016.1206817","article-title":"Dorsal root ganglion stimulation approval by the Food and Drug Administration: Advice on evolving the process","volume":"16","author":"Deer","year":"2016","journal-title":"Expert Rev. Neurother."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1111\/papr.13255","article-title":"Dorsal Root Ganglion Stimulation for the Treatment of Chronic Pelvic Pain: A Systematic Review","volume":"23","author":"Ghorayeb","year":"2023","journal-title":"Pain Pract."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s11916-022-01035-9","article-title":"Neuromodulation Interventions for the Treatment of Painful Diabetic Neuropathy: A Systematic Review","volume":"26","author":"Langford","year":"2022","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_52","unstructured":"Elsayed, A.A., Moghim, R., and Reffat, N. (Pain Pract., 2024). Dorsal Root Ganglion Stimulation (DRG-s) for Potential Resolution of Restless Leg Syndrome Symptoms and Increased Cost Savings for Patients: A Case Study, Pain Pract., Epub ahead of print."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"925","DOI":"10.2147\/JPR.S355096","article-title":"Diagnosis, Treatment, and Management of Painful Scar: A Narrative Review","volume":"15","author":"Pope","year":"2022","journal-title":"J. Pain Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1093\/pm\/pnw075","article-title":"Treatment of FBSS low back pain with a novel percutaneous DRG wireless stimulator: Pilot and feasibility study","volume":"17","author":"Weiner","year":"2016","journal-title":"Pain Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1111\/papr.12591","article-title":"Stimulation of the L2-L3 dorsal root ganglia induces effective pain relief in the low back","volume":"18","author":"Huygen","year":"2018","journal-title":"Pain Pract."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1111\/pme.12413","article-title":"The Role of the Dorsal Root Ganglion in the Development of Neuropathic Pain","volume":"15","author":"Krames","year":"2014","journal-title":"Pain Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1002\/ar.1091760209","article-title":"Axon Diameter and Myelin Thickness\u2014Unusual Relationships in Dorsal Root Ganglia","volume":"176","author":"Spencer","year":"1973","journal-title":"Anat. Rec."},{"key":"ref_58","first-page":"223","article-title":"Dorsal Root Ganglion: A Key to Understanding the Therapeutic Effects of the Erector Spinae Plane (ESP) and Other Intertransverse Process Blocks?","volume":"49","author":"Leonardsen","year":"2023","journal-title":"Reg. Anesthesia Pain Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1113\/jphysiol.2012.242750","article-title":"Failure of Action Potential Propagation in Sensory Neurons: Mechanisms and Loss of Afferent Filtering in C-Type Units after Painful Nerve Injury","volume":"591","author":"Gemes","year":"2013","journal-title":"J. Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1016\/S0006-3495(03)75024-3","article-title":"Electrical Excitability of the SOMA of Sensory Neurons Is Required for Spike Invasion of the SOMA, but Not for Through-Conduction","volume":"84","author":"Amir","year":"2003","journal-title":"Biophys. J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3140","DOI":"10.1152\/jn.00226.2015","article-title":"Spike Propagation through the Dorsal Root Ganglia in an Unmyelinated Sensory Neuron: A Modeling Study","volume":"114","author":"Sundt","year":"2015","journal-title":"J. Neurophysiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1146\/annurev-neuro-080317-061522","article-title":"Endogenous and Exogenous Opioids in Pain","volume":"41","author":"Corder","year":"2018","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1111\/ner.13150","article-title":"The Pathways and Processes Underlying Spinal Transmission of Low Back Pain: Observations From Dorsal Root Ganglion Stimulation Treatment","volume":"24","author":"Chapman","year":"2021","journal-title":"Neuromodulation"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4440","DOI":"10.1007\/s12325-022-02244-9","article-title":"Dorsal Root Ganglion Stimulation for Lower Extremity Neuropathic Pain Syndromes: An Evidence-Based Literature Review","volume":"39","author":"Kubrova","year":"2022","journal-title":"Adv. Ther."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.jpain.2021.07.008","article-title":"Dorsal Root Ganglion Stimulation for Chronic Pain: Hypothesized Mechanisms of Action","volume":"23","author":"Graham","year":"2022","journal-title":"J. Pain"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1111\/ner.12028","article-title":"Effect of Electrical Field Stimulation on Dorsal Root Ganglion Neuronal Function","volume":"16","author":"Koopmeiners","year":"2013","journal-title":"Neuromodul. Technol. Neural Interface"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1002\/cne.902220402","article-title":"A Study of Axonal Diameters and Areas in Lumbosacral Roots and Nerves in the Rat","volume":"222","author":"Suh","year":"1984","journal-title":"J. Comp. Neurol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1152\/jn.2001.85.1.197","article-title":"Computer Model for Action Potential Propagation through Branch Point in Myelinated Nerves","volume":"85","author":"Liu","year":"2001","journal-title":"J. Neurophysiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"RC43","DOI":"10.1523\/JNEUROSCI.19-24-j0001.1999","article-title":"A Novel Persistent Tetrodotoxin-Resistant Sodium Current in SNS-Null and Wild-Type Small Primary Sensory Neurons","volume":"19","author":"Cummins","year":"1999","journal-title":"J. Neurosci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3347","DOI":"10.1152\/jn.1999.82.6.3347","article-title":"Mechanical and Thermal Hyperalgesia and Ectopic Neuronal Discharge after Chronic Compression of Dorsal Root Ganglia","volume":"82","author":"Song","year":"1999","journal-title":"J. Neurophysiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1523\/JNEUROSCI.22-03-01187.2002","article-title":"Burst Discharge in Primary Sensory Neurons: Triggered by Subthreshold Oscillations, Maintained by Depolarizing Afterpotentials","volume":"22","author":"Amir","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"8589","DOI":"10.1523\/JNEUROSCI.19-19-08589.1999","article-title":"Membrane Potential Oscillations in Dorsal Root Ganglion Neurons: Role in Normal Electrogenesis and Neuropathic Pain","volume":"19","author":"Amir","year":"1999","journal-title":"J. Neurosci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1152\/jn.00005.2009","article-title":"Simulation in Sensory Neurons Reveals a Key Role for Delayed NA+ Current in Subthreshold Oscillations and Ectopic Discharge: Implications for Neuropathic Pain","volume":"102","author":"Kovalsky","year":"2009","journal-title":"J. Neurophysiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.jpain.2006.01.444","article-title":"The Role of Sodium Channels in Chronic Inflammatory and Neuropathic Pain","volume":"7","author":"Amir","year":"2006","journal-title":"J. Pain"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2576","DOI":"10.1523\/JNEUROSCI.4118-04.2005","article-title":"Multiple Interacting Sites of Ectopic Spike Electrogenesis in Primary Sensory Neurons","volume":"25","author":"Amir","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"14059","DOI":"10.1523\/JNEUROSCI.3699-07.2007","article-title":"Multiple Sites for Generation of Ectopic Spontaneous Activity in Neurons of the Chronically Compressed Dorsal Root Ganglion","volume":"27","author":"Ma","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1093\/brain\/awf037","article-title":"Oscillatory Mechanism in Primary Sensory Neurones","volume":"125","author":"Amir","year":"2002","journal-title":"Brain"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/0304-3959(88)90027-9","article-title":"Myelinated Afferents Signal the Hyperalgesia Associated with Nerve Injury","volume":"32","author":"Campbell","year":"1988","journal-title":"Pain"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"641588","DOI":"10.3389\/fimmu.2021.641588","article-title":"Role of Peripheral Immune Cells for Development and Recovery of Chronic Pain","volume":"12","author":"Bethea","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_80","first-page":"35","article-title":"Association of neural inflammation with hyperalgesia following spinal nerve ligation","volume":"48","author":"Znaor","year":"2007","journal-title":"Croat. Med. J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/s41583-020-0333-z","article-title":"Emerging Importance of Satellite Glia in Nervous System Function and Dysfunction","volume":"21","author":"Hanani","year":"2020","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/0304-3940(92)90170-C","article-title":"Mutual Excitation among Dorsal Root Ganglion Neurons in the Rat","volume":"146","author":"Utzschneider","year":"1992","journal-title":"Neurosci. Lett."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Mohr, K.M., Pallesen, L.T., Richner, M., and V\u00e6gter, C.B. (2021). Discrepancy in the Usage of GFAP as a Marker of Satellite Glial Cell Reactivity. Biomedicines, 9.","DOI":"10.3390\/biomedicines9081022"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"49.e1","DOI":"10.1016\/j.ejpain.2009.02.005","article-title":"Gap Junctions in Dorsal Root Ganglia: Possible Contribution to Visceral Pain","volume":"14","author":"Huang","year":"2010","journal-title":"Eur. J. Pain"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1017\/S1740925X10000074","article-title":"Satellite Glial Cells Express IL-6 and Corresponding Signal-Transducing Receptors in the Dorsal Root Ganglia of Rat Neuropathic Pain Model","volume":"6","year":"2010","journal-title":"Neuron Glia Biol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"11193","DOI":"10.1073\/pnas.1307445110","article-title":"Fractalkine Mediates Inflammatory Pain through Activation of Satellite Glial Cells","volume":"110","author":"Talbot","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1002\/eji.201746989","article-title":"Satellite Glial Cells in Human Trigeminal Ganglia Have a Broad Expression of Functional Toll-like Receptors","volume":"47","author":"Mitterreiter","year":"2017","journal-title":"Eur. J. Immunol."},{"key":"ref_88","first-page":"296","article-title":"The Dorsal Root Ganglion as a Target for Neurorestoration in Neuropathic Pain","volume":"19","author":"Evercooren","year":"2023","journal-title":"Neural Regen. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s00281-017-0669-2","article-title":"Origins of Antidromic Activity in Sensory Afferent Fibers and Neurogenic Inflammation","volume":"40","author":"Sorkin","year":"2018","journal-title":"Semin. Immunopathol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2901","DOI":"10.1523\/JNEUROSCI.12-08-02901.1992","article-title":"Synaptic interactions between GABA- immunoreactive profiles and the terminals of functionally defined myelinated nociceptors in the monkey and cat spinal cord","volume":"12","author":"Alvarez","year":"1992","journal-title":"J. Neurosci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/978-3-662-46450-2_9","article-title":"Plasticity of inhibition in the spinal cord","volume":"Volume 227","author":"Todd","year":"2015","journal-title":"Pain Control. Handbook of Experimental Pharmacology"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1152\/jn.1938.1.4.378","article-title":"Reflex discharge from the spinal cord over the dorsal roots","volume":"1","author":"Toennies","year":"1938","journal-title":"J. Neurophysiol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/1742-2094-8-20","article-title":"Differential Contribution of Electrically Evoked Dorsal Root Reflexes to Peripheral Vasodilatation and Plasma Extravasation","volume":"8","author":"Lobanov","year":"2011","journal-title":"J. Neuroinflamm."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/s002210050637","article-title":"Dorsal root potentials and dorsal root reflexes: A double-edged sword","volume":"124","author":"Willis","year":"1999","journal-title":"Exp. Brain Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"839","DOI":"10.2147\/JPR.S364370","article-title":"Best Practices for Dorsal Root Ganglion Stimulation for Chronic Pain: Guidelines from the American Society of Pain and Neuroscience","volume":"16","author":"Chapman","year":"2023","journal-title":"J. Pain Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1172\/JCI86812","article-title":"Local GABAergic Signaling within Sensory Ganglia Controls Peripheral Nociceptive Transmission","volume":"127","author":"Du","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s11916-012-0260-4","article-title":"Spinal Cord Stimulation: Neurophysiological and Neurochemical Mechanisms of Action","volume":"16","author":"Guan","year":"2012","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1097\/00006123-199608000-00026","article-title":"Release of Gamma-Aminobutyric Acid in the Dorsal Horn and Suppression of Tactile Allodynia by Spinal Cord Stimulation in Mononeuropathic Rats","volume":"39","author":"Stiller","year":"1996","journal-title":"Neurosurgery"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.neuroscience.2011.03.060","article-title":"Differential GABAergic Disinhibition during the Development of Painful Peripheral Neuropathy","volume":"184","author":"Janssen","year":"2011","journal-title":"Neuroscience"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.neuint.2011.11.006","article-title":"Decreased Intracellular GABA Levels Contribute to Spinal Cord Stimulation-Induced Analgesia in Rats Suffering from Painful Peripheral Neuropathy: The Role of KCC2 and GABAA Receptor-Mediated Inhibition","volume":"60","author":"Janssen","year":"2012","journal-title":"Neurochem. Int."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1111\/j.1533-2500.2012.00579.x","article-title":"Experimental Spinal Cord Stimulation and Neuropathic Pain: Mechanism of Action, Technical Aspects, and Effectiveness","volume":"13","author":"Smits","year":"2012","journal-title":"Pain Pract."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"6724","DOI":"10.1523\/JNEUROSCI.22-15-06724.2002","article-title":"Partial Peripheral Nerve Injury Promotes a Selective Loss of GABAergic Inhibition in the Superficial Dorsal Horn of the Spinal Cord","volume":"22","author":"Moore","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/S0304-3959(00)00404-8","article-title":"The Effects of GABAB Agonists and Gabapentin on Mechanical Hyperalgesia in Models of Neuropathic and Inflammatory Pain in the Rat","volume":"90","author":"Patel","year":"2001","journal-title":"Pain"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0304-3940(02)00157-X","article-title":"Dorsal Horn Synaptosomal Content of Aspartate, Glutamate, Glycine and GABA Are Differentially Altered Following Chronic Constriction Injury to the Rat Sciatic Nerve","volume":"323","author":"Somers","year":"2002","journal-title":"Neurosci. Lett."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.pain.2004.02.007","article-title":"Mechanical Allodynia Following Contusion Injury of the Rat Spinal Cord Is Associated with Loss of GABAergic Inhibition in the Dorsal Horn","volume":"109","author":"Drew","year":"2004","journal-title":"Pain"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.neuroimage.2016.11.046","article-title":"Dorsal Root Ganglion Stimulation Attenuates the BOLD Signal Response to Noxious Sensory Input in Specific Brain Regions: Insights into a Possible Mechanism for Analgesia","volume":"147","author":"Pawela","year":"2017","journal-title":"NeuroImage"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1111\/ner.13095","article-title":"Metabolic Imaging of Pain Matrix Using 18F Fluoro-Deoxyglucose Positron Emission Tomography\/Computed Tomography for Patients Undergoing L2 Dorsal Root Ganglion Stimulation for Low Back Pain","volume":"23","author":"Mehta","year":"2020","journal-title":"Neuromodulation"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/ner.12900","article-title":"Neurophysiological Effects of Dorsal Root Ganglion Stimulation (DRGS) in Pain Processing at the Cortical Level","volume":"22","author":"Morgalla","year":"2019","journal-title":"Neuromodul. Technol. Neural Interface"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Goudman, L., De Groote, S., Linderoth, B., De Smedt, A., Eldabe, S., Duarte, R., and Moens, M. (2021). Exploration of the Supraspinal Hypotheses about Spinal Cord Stimulation and Dorsal Root Ganglion Stimulation: A Systematic Review. J. Clin. Med., 10.","DOI":"10.3390\/jcm10132766"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1111\/ner.12921","article-title":"Dorsal Root Ganglion Stimulation Is Paresthesia-Independent: A Retrospective Study","volume":"22","author":"Verrills","year":"2019","journal-title":"Neuromodulation"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.2147\/JPR.S207610","article-title":"Voltage Gated Sodium Channels as Therapeutic Targets for Chronic Pain","volume":"12","author":"Yu","year":"2019","journal-title":"J. Pain Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"566418","DOI":"10.3389\/fncel.2020.566418","article-title":"K+ Channels in Primary Afferents and Their Role in Nerve Injury-Induced Pain","volume":"14","author":"Smith","year":"2020","journal-title":"Front. Cell. Neurosci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"54","DOI":"10.3389\/fphar.2011.00054","article-title":"Recent Developments Regarding Voltage-Gated Sodium Channel Blockers for the Treatment of Inherited and Acquired Neuropathic Pain Syndromes","volume":"2","author":"Theile","year":"2011","journal-title":"Front. Pharmacol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/S0006-8993(99)02165-4","article-title":"Ectopic Discharges and Adrenergic Sensitivity of Sensory Neurons after Spinal Nerve Injury","volume":"849","author":"Liu","year":"1999","journal-title":"Brain Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"833104","DOI":"10.3389\/fpain.2022.833104","article-title":"The Path to Discovery of Windup and Central Sensitization","volume":"3","author":"Mendell","year":"2022","journal-title":"Front. Pain Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/0304-3940(92)90920-3","article-title":"Spontaneous Discharge Originates in the Dorsal Root Ganglion at the Onset of a Painful Peripheral Neuropathy in the Rat","volume":"138","author":"Kajander","year":"1992","journal-title":"Neurosci. Lett."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1111\/ner.12754","article-title":"Mechanisms of Dorsal Root Ganglion Stimulation in Pain Suppression: A Computational Modeling Analysis","volume":"21","author":"Kent","year":"2018","journal-title":"Neuromodulation"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1016\/j.clinph.2003.12.024","article-title":"Uncovering the Mechanism(s) of Action of Deep Brain Stimulation: Activation, Inhibition, or Both","volume":"115","author":"McIntyre","year":"2004","journal-title":"Clin. Neurophysiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/7\/3591\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:18:07Z","timestamp":1760105887000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/7\/3591"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,22]]},"references-count":118,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["ijms25073591"],"URL":"https:\/\/doi.org\/10.3390\/ijms25073591","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,22]]}}}