{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:48:52Z","timestamp":1791895732800,"version":"4.3.4"},"reference-count":92,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Misr International University"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurochem Res"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Neuroimaging implicates the medial prefrontal cortex (mPFC) and insula in fibromyalgia (FM), but synaptic and network mechanisms are unclear. To verify mPFC hypersynapticity in a reserpine-induced FM model and test whether anterior insular deep brain stimulation (DBS) restores mPFC oscillations and pain behavior. Thirty-six male Sprague\u2013Dawley rats received reserpine (1\u00a0mg\u00b7kg\u207b\u00b9 i.p., days 1\u20133) or vehicle. For Objective 1, mPFC tissue was analyzed by ELISA for glutamate, \u03b3-aminobutyric acid (GABA), C-FOS, nerve growth factor (NGF), synaptophysin, and postsynaptic density protein-95 (PSD-95). For Objective 2, rats were assigned to control-sham, control-DBS, FM-sham, or FM-DBS. Monopolar DBS (130\u00a0Hz, 60 \u00b5s, 100 \u00b5A; 15\u00a0min\u00b7day\u207b\u00b9 for 3 days) targeted the anterior insula; local field potentials were recorded from mPFC, and thermal nociception was assessed by tail immersion and hot-plate tests. Reserpine increased glutamate, C-FOS, NGF, synaptophysin, and PSD-95 and reduced GABA (all\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), confirming hypersynapticity. Insular DBS increased delta-band normalized ratios (NR) in FM and controls (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001), normalized FM-associated theta reductions, decreased alpha\/beta NR in controls, and suppressed elevated gamma NR in FM (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001). DBS increased withdrawal latencies in FM, indicating improved pain thresholds (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Reserpine induces biochemical hypersynapticity in mPFC, and brief anterior insular DBS rebalances mPFC oscillations and alleviates hyperalgesia. Insular DBS may correct cortical network dysfunction in FM.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s11064-025-04617-2","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T09:44:47Z","timestamp":1765446287000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Role of Insular Cortex and Prefrontal Cortex in the Pathogenesis of Fibromyalgia: Biochemical and Electrophysiological Rodent Study"],"prefix":"10.1007","volume":"51","author":[{"given":"Ahmed F.","family":"Abouelnaga","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelaziz M.","family":"Hussein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa","family":"Abass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mena Z.","family":"Shafiek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hala F.","family":"Zaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed F.","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weam W.","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,11]]},"reference":[{"key":"4617_CR1","doi-asserted-by":"publisher","first-page":"3891","DOI":"10.3390\/ijms22083891","volume":"22","author":"R Siracusa","year":"2021","unstructured":"Siracusa R, Di Paola R, Cuzzocrea S, Impellizzeri D (2021) Fibromyalgia, pathogenesis, mechanisms, diagnosis and treatment options update. Int J Mol Sci 22:3891","journal-title":"Int J Mol Sci"},{"key":"4617_CR2","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/426130","author":"E Bellato","year":"2012","unstructured":"Bellato E, Marini E, Castoldi F, Barbasetti N, Mattei L, Bonasia DE et al (2012) Fibromyalgia syndrome: etiology, pathogenesis, diagnosis, and treatment. Pain Res Treat. https:\/\/doi.org\/10.1155\/2012\/426130","journal-title":"Pain Res Treat"},{"key":"4617_CR3","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1016\/j.jpain.2014.04.007","volume":"15","author":"E Ichesco","year":"2014","unstructured":"Ichesco E, Schmidt-Wilcke T, Bhavsar R, Clauw DJ, Peltier SJ, Kim J et al (2014) Altered resting state connectivity of the insular cortex in individuals with fibromyalgia. J Pain Churchill Livingstone 15:815-826.e1","journal-title":"J Pain Churchill Livingstone"},{"key":"4617_CR4","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.jocn.2016.12.014","volume":"38","author":"P Sawaddiruk","year":"2017","unstructured":"Sawaddiruk P, Paiboonworachat S, Chattipakorn N, Chattipakorn SC (2017) Alterations of brain activity in fibromyalgia patients. J Clin Neurosci Churchill Livingstone 38:13\u201322","journal-title":"J Clin Neurosci Churchill Livingstone"},{"key":"4617_CR5","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.semarthrit.2006.12.009","volume":"36","author":"MB Yunus","year":"2007","unstructured":"Yunus MB (2007) Fibromyalgia and overlapping disorders: the unifying concept of central sensitivity syndromes. Semin Arthritis Rheum 36:339\u2013356","journal-title":"Semin Arthritis Rheum"},{"key":"4617_CR6","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.jpain.2019.06.013","volume":"21","author":"AP Brietzke","year":"2020","unstructured":"Brietzke AP, Zortea M, Carvalho F, Sanches PRS, Silva DPJ, Torres IL da (2020) Large treatment effect with extended Home-Based transcranial direct current stimulation over dorsolateral prefrontal cortex in fibromyalgia: A proof of concept Sham-Randomized clinical study. J Pain Churchill Livingstone 21:212\u2013224","journal-title":"J Pain Churchill Livingstone"},{"key":"4617_CR7","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.neuroimage.2014.01.020","volume":"91","author":"SJ Thompson","year":"2014","unstructured":"Thompson SJ, Millecamps M, Aliaga A, Seminowicz DA, Low LA, Bedell BJ et al (2014) Metabolic brain activity suggestive of persistent pain in a rat model of neuropathic pain. Neuroimage Acad Press 91:344\u2013352","journal-title":"Neuroimage Acad Press"},{"key":"4617_CR8","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.pain.2013.10.026","volume":"155","author":"KL Hung","year":"2014","unstructured":"Hung KL, Wang SJ, Wang YC, Chiang TR, Wang CC (2014) Upregulation of presynaptic proteins and protein kinases associated with enhanced glutamate release from axonal terminals (synaptosomes) of the medial prefrontal cortex in rats with neuropathic pain. Pain 155:377\u2013387","journal-title":"Pain"},{"key":"4617_CR9","doi-asserted-by":"publisher","first-page":"2423","DOI":"10.1073\/pnas.0809897106","volume":"106","author":"AE Metz","year":"2009","unstructured":"Metz AE, Yau HJ, Centeno MV, Apkarian AV, Martina M (2009) Morphological and functional reorganization of rat medial prefrontal cortex in neuropathic pain. Proc Natl Acad Sci 106:2423\u20132428","journal-title":"Proc Natl Acad Sci"},{"key":"4617_CR10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1744-8069-10-63","volume":"10","author":"HC Lin","year":"2014","unstructured":"Lin HC, Huang YH, Chao THH, Lin WY, Sun WZ, Yen CT (2014) Gabapentin reverses central hypersensitivity and suppresses medial prefrontal cortical glucose metabolism in rats with neuropathic pain. Mol Pain 10:1\u201312","journal-title":"Mol Pain"},{"key":"4617_CR11","doi-asserted-by":"publisher","first-page":"1926","DOI":"10.1126\/science.1099745","volume":"304","author":"G Buzs\u00e1ki","year":"2004","unstructured":"Buzs\u00e1ki G, Draguhn A (2004) Neuronal oscillations in cortical networks. Science 304:1926\u20131929","journal-title":"Science"},{"key":"4617_CR12","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD008208.pub4","author":"NE O\u2019Connell","year":"2018","unstructured":"O\u2019Connell NE, Marston L, Spencer S, Desouza LH (2018) Wand BM Non-invasive brain stimulation techniques for chronic pain. Cochrane Database Syst Rev. https:\/\/doi.org\/10.1002\/14651858.CD008208.pub4","journal-title":"Cochrane Database Syst Rev"},{"key":"4617_CR13","doi-asserted-by":"publisher","first-page":"2111","DOI":"10.1016\/S0140-6736(21)00794-7","volume":"397","author":"H Knotkova","year":"2021","unstructured":"Knotkova H, Hamani C, Sivanesan E, Le Beuffe MFE, Moon JY (2021) Cohen SP Neuromodulation for chronic pain. Lancet 397:2111\u20132124","journal-title":"Lancet"},{"key":"4617_CR14","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1016\/j.neuron.2011.11.006","volume":"72","author":"H Lind\u00e9n","year":"2011","unstructured":"Lind\u00e9n H, Tetzlaff T, Potjans TC, Pettersen KH, Gr\u00fcn S, Diesmann M et al (2011) Modeling the spatial reach of the LFP. Neuron 72:859\u2013872","journal-title":"Neuron"},{"key":"4617_CR15","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1038\/nrn3241","volume":"13","author":"G Buzs\u00e1ki","year":"2012","unstructured":"Buzs\u00e1ki G, Anastassiou CA, Koch C (2012) The origin of extracellular fields and currents \u2014 EEG, ECoG, LFP and spikes. Nat Rev Neurosci 13:407\u2013420","journal-title":"Nat Rev Neurosci"},{"key":"4617_CR16","unstructured":"Mazzoni A, Logothetis NK, Panzeri S (2012) The information content of Local Field Potentials: experiments and models. Princ Neural Coding. CRC Press, pp 411\u2013430. Available from: https:\/\/arxiv.org\/abs\/1206.0560v1"},{"key":"4617_CR17","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1002\/hipo.22255","volume":"24","author":"R Kaplan","year":"2014","unstructured":"Kaplan R, Bush D, Bonnefond M, Bandettini PA, Barnes GR, Doeller CF et al (2014) Medial prefrontal theta phase coupling during spatial memory retrieval. Hippocampus 24:656\u2013665","journal-title":"Hippocampus"},{"key":"4617_CR18","doi-asserted-by":"publisher","first-page":"14211","DOI":"10.1523\/JNEUROSCI.2378-13.2013","volume":"33","author":"PK O\u2019Neill","year":"2013","unstructured":"O\u2019Neill PK, Gordon JA, Sigurdsson T (2013) Theta oscillations in the medial prefrontal cortex are modulated by spatial working memory and synchronize with the hippocampus through its ventral subregion. J Neurosci 33:14211\u201314224","journal-title":"J Neurosci"},{"key":"4617_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.7554\/eLife.55585","volume":"9","author":"DA Gehrlach","year":"2020","unstructured":"Gehrlach DA, Weiand C, Gaitanos TN, Cho E, Klein AS, Hennrich AA et al (2020) A whole-brain connectivity map of mouse insular cortex. Elife 9:1\u201378","journal-title":"Elife"},{"key":"4617_CR20","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/nrn2555","volume":"10","author":"AD Craig","year":"2009","unstructured":"Craig AD (2009) How do you feel \u2014 now? The anterior insula and human awareness. Nat Rev Neurosci 10:59\u201370","journal-title":"Nat Rev Neurosci"},{"key":"4617_CR21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-020-79371-2","volume":"10","author":"G Liberati","year":"2020","unstructured":"Liberati G, Mulders D, Algoet M, van den Broeke EN, Santos SF, Ribeiro Vaz JG et al (2020) Insular responses to transient painful and non-painful thermal and mechanical spinothalamic stimuli recorded using intracerebral EEG. Sci Rep 10:1\u201315","journal-title":"Sci Rep"},{"key":"4617_CR22","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1152\/jn.91100.2008","volume":"101","author":"MN Baliki","year":"2009","unstructured":"Baliki MN, Geha PY, Apkarian AV (2009) Parsing pain perception between nociceptive representation and magnitude estimation. J Neurophysiol 101:875\u2013887","journal-title":"J Neurophysiol"},{"key":"4617_CR23","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1016\/S0072-9752(06)80052-7","volume":"81","author":"J Boivie","year":"2006","unstructured":"Boivie J (2006) Chapter 48 central post-stroke pain. Handb Clin Neurol Elsevier 81:715\u2013730","journal-title":"Handb Clin Neurol Elsevier"},{"key":"4617_CR24","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/0304-3959(95)00048-W","volume":"63","author":"JC Hsieh","year":"1995","unstructured":"Hsieh JC, Belfrage M, Stone-Elander S, Hansson P, Ingvar M (1995) Central representation of chronic ongoing neuropathic pain studied by positron emission tomography. Pain 63:225\u2013236","journal-title":"Pain"},{"key":"4617_CR25","doi-asserted-by":"publisher","first-page":"5956","DOI":"10.1523\/JNEUROSCI.5980-10.2011","volume":"31","author":"MG Murray","year":"2011","unstructured":"Murray MG, Gustin SM, Peck CC, Wilcox LS, Henderson LA, Nash GP (2011) Different pain, different brain: thalamic anatomy in neuropathic and non-neuropathic chronic pain syndromes. J Neurosci 31:5956\u20135964","journal-title":"J Neurosci"},{"key":"4617_CR26","doi-asserted-by":"publisher","first-page":"3146","DOI":"10.1002\/art.24849","volume":"60","author":"RE Harris","year":"2009","unstructured":"Harris RE, Sundgren PC, Craig AD, Kirshenbaum E, Sen A, Napadow V et al (2009) Elevated insular glutamate in fibromyalgia is associated with experimental pain. Arthritis Rheum 60:3146\u20133152","journal-title":"Arthritis Rheum"},{"key":"4617_CR27","doi-asserted-by":"publisher","first-page":"3650","DOI":"10.1093\/cercor\/bhx237","volume":"28","author":"G Liberati","year":"2018","unstructured":"Liberati G, Kl\u00f6cker A, Algoet M, Mulders D, Safronova MM, Santos SF et al (2018) Gamma-band oscillations preferential for nociception can be recorded in the human insula. Cereb Cortex 28:3650\u20133664","journal-title":"Cereb Cortex"},{"key":"4617_CR28","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1097\/j.pain.0000000000001707","volume":"161","author":"FB Pomares","year":"2020","unstructured":"Pomares FB, Roy S, Funck T, Feier NA, Thiel A, Fitzcharles MA et al (2020) Upregulation of cortical GABAA receptor concentration in fibromyalgia. Pain 161:74\u201382","journal-title":"Pain"},{"key":"4617_CR29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s10194-021-01377-6","volume":"23","author":"M Mozafarihashjin","year":"2022","unstructured":"Mozafarihashjin M, Togha M, Ghorbani Z, Farbod A, Rafiee P, Martami F (2022) Assessment of peripheral biomarkers potentially involved in episodic and chronic migraine: a case-control study with a focus on NGF, BDNF, VEGF, and PGE2. J Headache Pain 23:1\u201312","journal-title":"J Headache Pain"},{"key":"4617_CR30","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1515\/hsz-2016-0280","volume":"398","author":"C Montagnoli","year":"2017","unstructured":"Montagnoli C, Tiribuzi R, Crispoltoni L, Pistilli A, Stabile AM, Manfreda F et al (2017) \u03b2-NGF and \u03b2-NGF receptor upregulation in blood and synovial fluid in osteoarthritis. Biol Chem 398:1045\u20131054","journal-title":"Biol Chem"},{"key":"4617_CR31","doi-asserted-by":"publisher","first-page":"10443","DOI":"10.3390\/ijms241310443","volume":"24","author":"M Favretti","year":"2023","unstructured":"Favretti M, Iannuccelli C, Di Franco M (2023) Pain biomarkers in fibromyalgia syndrome: current understanding and future directions. Int J Mol Sci 24:10443","journal-title":"Int J Mol Sci"},{"key":"4617_CR32","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1111\/cns.12663","volume":"23","author":"PA Zhang","year":"2017","unstructured":"Zhang PA, Xu QY, Xue L, Zheng H, Yan J, Xiao Y et al (2017) Neonatal maternal deprivation enhances presynaptic P2X7 receptor transmission in insular cortex in an adult rat model of visceral hypersensitivity. CNS Neurosci Ther 23:145\u2013154","journal-title":"CNS Neurosci Ther"},{"key":"4617_CR33","doi-asserted-by":"publisher","DOI":"10.1177\/1744806918764731","author":"PA Zhang","year":"2018","unstructured":"Zhang PA, Zhu HY, Xu QY, Du WJ, Hu S, Xu GY (2018) Sensitization of P2X3 receptors in insular cortex contributes to visceral pain of adult rats with neonatal maternal deprivation. Mol Pain. https:\/\/doi.org\/10.1177\/1744806918764731","journal-title":"Mol Pain"},{"key":"4617_CR34","first-page":"1343","volume":"19","author":"X Yao","year":"2020","unstructured":"Yao X, Li L, Kandhare AD, Mukherjee-Kandhare AA, Bodhankar SL (2020) Attenuation of reserpine-induced fibromyalgia via ROS and serotonergic pathway modulation by fisetin, a plant flavonoid polyphenol. Exp Ther Med 19:1343","journal-title":"Exp Ther Med"},{"key":"4617_CR35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11481-025-10196-4","volume":"20","author":"MZ Shafiek","year":"2025","unstructured":"Shafiek MZ, Zaki HF, Mohamed AF, Ibrahim WW (2025) Novel trajectories towards possible effects of semaglutide for amelioration of reserpine-induced fibromyalgia in rats: contribution of cAMP\/PKA\/p-CREB and M1\/M2 microglia polarization. J Neuroimmune Pharmacol 20:1\u201313. https:\/\/doi.org\/10.1007\/s11481-025-10196-4","journal-title":"J Neuroimmune Pharmacol"},{"key":"4617_CR36","doi-asserted-by":"publisher","first-page":"118076","DOI":"10.1016\/j.lfs.2020.118076","volume":"257","author":"AE El-Sahar","year":"2020","unstructured":"El-Sahar AE, Rastanawi AA, El-Yamany MF, Saad MA (2020) Dapagliflozin improves behavioral dysfunction of Huntington\u2019s disease in rats via inhibiting apoptosis-related glycolysis. Life Sci 257:118076","journal-title":"Life Sci"},{"key":"4617_CR37","doi-asserted-by":"publisher","first-page":"6139","DOI":"10.3390\/ijms23116139","volume":"23","author":"M Cordaro","year":"2022","unstructured":"Cordaro M, Siracusa R, D\u2019amico R, Genovese T, Franco G, Marino Y et al (2022) Role of etanercept and infliximab on nociceptive changes induced by the experimental model of Fibromyalgia. Int J Mol Sci 23:6139","journal-title":"Int J Mol Sci"},{"key":"4617_CR38","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.neures.2022.03.005","volume":"181","author":"Y Ejiri","year":"2022","unstructured":"Ejiri Y, Uta D, Ota H, Mizumura K, Taguchi T (2022) Nociceptive chemical hypersensitivity in the spinal cord of a rat reserpine-induced fibromyalgia model. Neurosci Res 181:87\u201394","journal-title":"Neurosci Res"},{"key":"4617_CR39","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","volume":"72","author":"MM Bradford","year":"1976","unstructured":"Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem Acad Press 72:248\u2013254","journal-title":"Anal Biochem Acad Press"},{"key":"4617_CR40","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.13041","author":"MZ Shafiek","year":"2024","unstructured":"Shafiek MZ, Zaki HF, Mohamed AF (2024) New ways to repurpose salmeterol in an animal model of fibromyalgia. Fundam Clin Pharmacol. https:\/\/doi.org\/10.1111\/fcp.13041","journal-title":"Fundam Clin Pharmacol"},{"key":"4617_CR41","doi-asserted-by":"publisher","DOI":"10.3791\/3528","author":"RV Fornari","year":"2012","unstructured":"Fornari RV, Wichmann R, Atsak P, Atucha E, Barsegyan A, Beldjoud H et al (2012) Rodent stereotaxic surgery and animal welfare outcome improvements for behavioral neuroscience. J Vis Exp. https:\/\/doi.org\/10.3791\/3528","journal-title":"J Vis Exp"},{"key":"4617_CR42","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.bbr.2008.07.027","volume":"196","author":"ET Fonoff","year":"2009","unstructured":"Fonoff ET, Dale CS, Pagano RL, Paccola CC, Ballester G, Teixeira MJ et al (2009) Antinociception induced by epidural motor cortex stimulation in Naive conscious rats is mediated by the opioid system. Behav Brain Res 196:63\u201370","journal-title":"Behav Brain Res"},{"key":"4617_CR43","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.643384","volume":"15","author":"C Silva","year":"2021","unstructured":"Silva C, Porter BS, Hillman KL (2021) Stimulation in the rat anterior insula and anterior cingulate during an effortful weightlifting task. Front Neurosci 15:643384","journal-title":"Front Neurosci"},{"key":"4617_CR44","doi-asserted-by":"publisher","DOI":"10.1177\/1744806918785686","author":"B Fu","year":"2018","unstructured":"Fu B, Wen SN, Wang B, Wang K, Zhang JY, Liu SJ (2018) Acute and chronic pain affects local field potential of the medial prefrontal cortex in different band neural oscillations. Mol Pain. https:\/\/doi.org\/10.1177\/1744806918785686","journal-title":"Mol Pain"},{"key":"4617_CR45","first-page":"48","volume":"7","author":"M Abo-Zahhad","year":"2015","unstructured":"Abo-Zahhad M, Ahmed SM, Abbas SN (2015) A new EEG acquisition protocol for biometric identification using eye blinking signals. Int J Intell Syst Appl 7:48\u201354","journal-title":"Int J Intell Syst Appl"},{"key":"4617_CR46","doi-asserted-by":"publisher","first-page":"284","DOI":"10.3389\/fnmol.2017.00284","volume":"10","author":"JR Deuis","year":"2017","unstructured":"Deuis JR, Dvorakova LS, Vetter I (2017) Methods used to evaluate pain behaviors in rodents. Front Mol Neurosci 10:284","journal-title":"Front Mol Neurosci"},{"key":"4617_CR47","doi-asserted-by":"publisher","first-page":"271711","DOI":"10.3389\/fnmol.2017.00284","volume":"10","author":"JR Deuis","year":"2017","unstructured":"Deuis JR, Dvorakova LS, Vetter I (2017) Methods used to evaluate pain behaviors in rodents. Front Mol Neurosci 10:271711","journal-title":"Front Mol Neurosci"},{"key":"4617_CR48","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-10-41","author":"H Leite-Almeida","year":"2014","unstructured":"Leite-Almeida H, Guimar\u00e3es MR, Cerqueira JJ, Ribeiro-Costa N, Anjos-Martins H, Sousa N et al (2014) Asymmetric c-fos expression in the ventral orbital cortex is associated with impaired reversal learning in a right-sided neuropathy. Mol Pain. https:\/\/doi.org\/10.1186\/1744-8069-10-41","journal-title":"Mol Pain"},{"issue":"6131","key":"4617_CR49","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1038\/328632a0","volume":"328","author":"SP Hunt","year":"1987","unstructured":"Hunt SP, Pini A, Evan G (1987) Induction of c-fos-like protein in spinal cord neurons following sensory stimulation. Nature 328(6131):632\u2013634","journal-title":"Nature"},{"key":"4617_CR50","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/S0306-4522(02)00153-7","volume":"113","author":"QP Wang","year":"2002","unstructured":"Wang QP, Zadina JE, Guan JL, Kastin AJ, Funahashi H, Shioda S (2002) Endomorphin-2 immunoreactivity in the cervical dorsal horn of the rat spinal cord at the electron microscopic level. Neuroscience 113:593\u2013605","journal-title":"Neuroscience"},{"key":"4617_CR51","doi-asserted-by":"publisher","first-page":"1364","DOI":"10.1126\/science.290.5495.1364","volume":"290","author":"AE-D El-Husseini","year":"2000","unstructured":"El-Husseini AE-D, Schnell E, Chetkovich DM, Nicoll RA, Bredt DS (2000) PSD-95 involvement in maturation of excitatory synapses. Science 290:1364\u20131368. https:\/\/doi.org\/10.1126\/science.290.5495.1364","journal-title":"Science"},{"key":"4617_CR52","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.neures.2020.05.010","volume":"166","author":"X Zhang","year":"2021","unstructured":"Zhang X, Li X, Wang H, Xie X, Li Y, Xu X et al (2021) Shank3 contributes to neuropathic pain by facilitating the SNI-dependent increase of HCN2 and the expression of PSD95. Neurosci Res 166:34\u201341","journal-title":"Neurosci Res"},{"key":"4617_CR53","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13041-018-0398-z","volume":"11","author":"THH Chao","year":"2018","unstructured":"Chao THH, Chen JH, Yen CT (2018) Plasticity changes in forebrain activity and functional connectivity during neuropathic pain development in rats with sciatic spared nerve injury. Mol Brain 11:1\u201316","journal-title":"Mol Brain"},{"key":"4617_CR54","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1113\/jphysiol.2002.031369","volume":"546","author":"JC B\u00e9\u00efque","year":"2003","unstructured":"B\u00e9\u00efque JC, Andrade R (2003) PSD-95 regulates synaptic transmission and plasticity in rat cerebral cortex. J Physiol 546:859\u2013867","journal-title":"J Physiol"},{"key":"4617_CR55","doi-asserted-by":"publisher","first-page":"2117","DOI":"10.1089\/neu.2018.6260","volume":"36","author":"LM Konan","year":"2019","unstructured":"Konan LM, Song H, Pentecost G, Fogwe D, Ndam T, Cui J et al (2019) Multi-focal neuronal ultrastructural abnormalities and synaptic alterations in mice after low-intensity blast exposure. J Neurotrauma 36:2117\u20132128","journal-title":"J Neurotrauma"},{"key":"4617_CR56","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.neuroscience.2017.02.055","volume":"349","author":"L Carey","year":"2017","unstructured":"Carey L, Lee WH, Gutierrez T, Kulkarni P, Thakur G, Lai Y et al (2017) Small molecule inhibitors of PSD95\u2013nNOS protein\u2013protein interactions suppress formalin-evoked Fos protein expression and nociceptive behavior in rats. Neuroscience 349:303\u2013317","journal-title":"Neuroscience"},{"key":"4617_CR57","doi-asserted-by":"publisher","first-page":"7574","DOI":"10.1523\/JNEUROSCI.0174-13.2013","volume":"33","author":"LA Henderson","year":"2013","unstructured":"Henderson LA, Peck CC, Petersen ET, Rae CD, Youssef AM, Reeves JM et al (2013) Chronic pain: lost inhibition? J Neurosci 33:7574\u20137582","journal-title":"J Neurosci"},{"key":"4617_CR58","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1097\/AJP.0000000000000474","volume":"33","author":"TL Pyke","year":"2017","unstructured":"Pyke TL, Osmotherly PG, Baines S (2017) Measuring glutamate levels in the brains of fibromyalgia patients and a potential role for glutamate in the pathophysiology of fibromyalgia symptoms. Clin J Pain 33:944\u2013954","journal-title":"Clin J Pain"},{"key":"4617_CR59","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1007\/s00221-015-4212-1","volume":"233","author":"LN Spezia Adachi","year":"2015","unstructured":"Spezia Adachi LN, Quevedo AS, de Souza A, Scarabelot VL, Rozisky JR, de Oliveira C et al (2015) Exogenously induced brain activation regulates neuronal activity by top-down modulation: conceptualized model for electrical brain stimulation. Exp Brain Res 233:1377\u20131389","journal-title":"Exp Brain Res"},{"key":"4617_CR60","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s10194-017-0799-x","volume":"18","author":"FJ Hsiao","year":"2017","unstructured":"Hsiao FJ, Wang SJ, Lin YY, Fuh JL, Ko YC, Wang PN et al (2017) Altered insula\u2013default mode network connectivity in fibromyalgia: a resting-state magnetoencephalographic study. J Headache Pain 18:1\u201310","journal-title":"J Headache Pain"},{"key":"4617_CR61","first-page":"364","volume":"31","author":"DB Cook","year":"2004","unstructured":"Cook DB, Lange G, Ciccone DS, Liu W-C, Steffener J, Natelson BH (2004) Functional imaging of pain in patients with primary fibromyalgia. J Rheumatol 31:364\u2013378","journal-title":"J Rheumatol"},{"key":"4617_CR62","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1002\/art.10225","volume":"46","author":"RH Gracely","year":"2002","unstructured":"Gracely RH, Petzke F, Wolf JM, Clauw DJ (2002) Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum 46:1333\u20131343","journal-title":"Arthritis Rheum"},{"key":"4617_CR63","doi-asserted-by":"publisher","first-page":"2545","DOI":"10.1002\/art.27497","volume":"62","author":"V Napadow","year":"2010","unstructured":"Napadow V, LaCount L, Park K, As-Sanie S, Clauw DJ, Harris RE (2010) Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity. Arthritis Rheum 62:2545\u201355","journal-title":"Arthritis Rheum"},{"key":"4617_CR64","doi-asserted-by":"publisher","first-page":"2398","DOI":"10.1002\/art.34412","volume":"64","author":"V Napadow","year":"2012","unstructured":"Napadow V, Kim J, Clauw DJ, Harris RE (2012) Brief Report: Decreased intrinsic brain connectivity is associated with reduced clinical pain in fibromyalgia. Arthritis Rheum 64:2398\u20132403","journal-title":"Arthritis Rheum"},{"key":"4617_CR65","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1089\/brain.2014.0274","volume":"4","author":"P Flodin","year":"2014","unstructured":"Flodin P, Martinsen S, L\u00f6fgren M, Bileviciute-Ljungar I, Kosek E, Fransson P (2014) Fibromyalgia is associated with decreased connectivity between pain-and sensorimotor brain areas. Brain Connect 4:587\u2013594. https:\/\/doi.org\/10.1089\/brain.2014.0274","journal-title":"Brain Connect"},{"key":"4617_CR66","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1016\/j.neuroimage.2012.09.030","volume":"64","author":"A Lutz","year":"2013","unstructured":"Lutz A, McFarlin DR, Perlman DM, Salomons TV, Davidson RJ (2013) Altered anterior insula activation during anticipation and experience of painful stimuli in expert meditators. Neuroimage 64:538\u2013546. https:\/\/doi.org\/10.1016\/j.neuroimage.2012.09.030","journal-title":"Neuroimage"},{"key":"4617_CR67","doi-asserted-by":"publisher","first-page":"9673","DOI":"10.1073\/pnas.0504136102","volume":"102","author":"MD Fox","year":"2005","unstructured":"Fox MD, Snyder AZ, Vincent JL, Corbetta M, Van Essen DC, Raichle ME (2005) The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci U S A 102:9673\u20139678. https:\/\/doi.org\/10.1073\/pnas.0504136102","journal-title":"Proc Natl Acad Sci U S A"},{"key":"4617_CR68","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1073\/pnas.98.2.676","volume":"98","author":"ME Raichle","year":"2001","unstructured":"Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA, Shulman GL (2001) A default mode of brain function. Proc Natl Acad Sci 98:676\u2013682","journal-title":"Proc Natl Acad Sci"},{"issue":"2","key":"4617_CR69","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.neulet.2012.05.001","volume":"520","author":"MA Farmer","year":"2012","unstructured":"Farmer MA, Baliki MN, Apkarian AV (2012) A dynamic network perspective of chronic pain. Neurosci Lett 520(2):197\u2013203","journal-title":"Neurosci Lett"},{"key":"4617_CR70","doi-asserted-by":"publisher","first-page":"1744","DOI":"10.1186\/1744-8069-8-32","volume":"8","author":"KB Jensen","year":"2012","unstructured":"Jensen KB, Loitoile R, Kosek E, Petzke F, Carville S, Fransson P et al (2012) Patients with fibromyalgia display less functional connectivity in the brain\u2019s pain inhibitory network. Mol Pain 8:1744\u20138069","journal-title":"Mol Pain"},{"key":"4617_CR71","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004542","volume":"4","author":"F Cauda","year":"2009","unstructured":"Cauda F, Sacco K, Duca S, Cocito D, D\u2019Agata F, Geminiani GC et al (2009) Altered resting state in diabetic neuropathic pain. PLoS One 4:e4542","journal-title":"PLoS One"},{"key":"4617_CR72","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1093\/cercor\/bhs065","volume":"23","author":"LJ Chang","year":"2013","unstructured":"Chang LJ, Yarkoni T, Khaw MW, Sanfey AG (2013) Decoding the role of the insula in human cognition: functional parcellation and large-scale reverse inference. Cerebral Cortex 23:739\u2013749","journal-title":"Cerebral Cortex"},{"key":"4617_CR73","doi-asserted-by":"publisher","first-page":"18692","DOI":"10.1073\/pnas.1312902110","volume":"110","author":"A Kucyi","year":"2013","unstructured":"Kucyi A, Salomons TV, Davis KD (2013) Mind wandering away from pain dynamically engages antinociceptive and default mode brain networks. Proc Natl Acad Sci U S A 110:18692\u201318697","journal-title":"Proc Natl Acad Sci U S A"},{"key":"4617_CR74","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.nicl.2013.07.011","volume":"3","author":"N Fallon","year":"2013","unstructured":"Fallon N, Alghamdi J, Chiu Y, Sluming V, Nurmikko T, Stancak A (2013) Structural alterations in brainstem of fibromyalgia syndrome patients correlate with sensitivity to mechanical pressure. NeuroImage Clin 3:163\u2013170","journal-title":"NeuroImage Clin"},{"key":"4617_CR75","doi-asserted-by":"crossref","unstructured":"Jensen KB, Loitoile R, Kosek E, Petzke F, Carville S, Fransson P, et al. Patients with fibromyalgia display less functional connectivity in the brain\u2019s pain inhibitory network. Mol Pain [Internet]. SAGE PublicationsSage CA: Los Angeles, CA; 2012 [cited 2025 Jan 26];8. Available from: https:\/\/journals.sagepub.com\/doi\/full\/10.1186\/1744-8069-8-32","DOI":"10.1186\/1744-8069-8-32"},{"key":"4617_CR76","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.pain.2006.02.012","volume":"123","author":"S Ohara","year":"2006","unstructured":"Ohara S, Crone NE, Weiss N, Lenz FA (2006) Analysis of synchrony demonstrates \u2018pain networks\u2019 defined by rapidly switching, task-specific, functional connectivity between pain-related cortical structures. Pain 123:244\u2013253","journal-title":"Pain"},{"key":"4617_CR77","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1002\/hbm.23107","volume":"37","author":"EB Liddle","year":"2016","unstructured":"Liddle EB, Price D, Palaniyappan L, Brookes MJ, Robson SE, Hall EL et al (2016) Abnormal salience signaling in schizophrenia: The role of integrative beta oscillations. Hum Brain Mapp 37:1361\u20131374","journal-title":"Hum Brain Mapp"},{"key":"4617_CR78","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.tics.2016.12.001","volume":"21","author":"M Ploner","year":"2017","unstructured":"Ploner M, Sorg C, Gross J (2017) Brain rhythms of pain. Trends Cogn Sci 21:100\u2013110","journal-title":"Trends Cogn Sci"},{"key":"4617_CR79","doi-asserted-by":"publisher","first-page":"420","DOI":"10.4236\/jbbs.2015.510040","volume":"5","author":"W Dimpfel","year":"2015","unstructured":"Dimpfel W, Schombert L (2015) Slow gamma activity of local field potentials (LFP) in the freely moving rat relates to movement. J Behav Brain Sci 5:420\u2013429","journal-title":"J Behav Brain Sci"},{"issue":"9","key":"4617_CR80","doi-asserted-by":"publisher","first-page":"2419","DOI":"10.1016\/j.celrep.2017.10.123","volume":"21","author":"JB Trimper","year":"2017","unstructured":"Trimper JB, Galloway CR, Jones AC, Mandi K, Manns JR (2017) Gamma oscillations in rat hippocampal subregions dentate gyrus, CA3, CA1, and subiculum underlie associative memory encoding. Cell Rep 21(9):2419\u20132432","journal-title":"Cell Rep"},{"key":"4617_CR81","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2021.785328","author":"TM Mokhothu","year":"2021","unstructured":"Mokhothu TM, Tanaka KZ (2021) Characterizing hippocampal oscillatory signatures underlying seizures in temporal lobe epilepsy. Front Behav Neurosci. https:\/\/doi.org\/10.3389\/fnbeh.2021.785328","journal-title":"Front Behav Neurosci"},{"key":"4617_CR82","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1002\/ejp.1076","volume":"22","author":"N Fallon","year":"2018","unstructured":"Fallon N, Chiu Y, Nurmikko T, Stancak A (2018) Altered theta oscillations in resting EEG of fibromyalgia syndrome patients. Eur J Pain 22:49\u201357","journal-title":"Eur J Pain"},{"key":"4617_CR83","doi-asserted-by":"publisher","first-page":"178762","DOI":"10.3389\/fnhum.2016.00111","volume":"10","author":"M Lim","year":"2016","unstructured":"Lim M, Kim JS, Kim DJ, Chung CK (2016) Increased low-and high-frequency oscillatory activity in the prefrontal cortex of fibromyalgia patients. Front Hum Neurosci 10:178762","journal-title":"Front Hum Neurosci"},{"key":"4617_CR84","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1016\/j.neuroimage.2005.12.042","volume":"31","author":"J Stern","year":"2006","unstructured":"Stern J, Jeanmonod D, Sarnthein J (2006) Persistent EEG overactivation in the cortical pain matrix of neurogenic pain patients. Neuroimage 31:721\u2013731","journal-title":"Neuroimage"},{"key":"4617_CR85","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1093\/brain\/awh631","volume":"129","author":"J Sarnthein","year":"2006","unstructured":"Sarnthein J, Stern J, Aufenberg C, Rousson V, Jeanmonod D (2006) Increased EEG power and slowed dominant frequency in patients with neurogenic pain. Brain 129:55\u201364","journal-title":"Brain"},{"key":"4617_CR86","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2005.12.042","author":"J Stern","year":"2006","unstructured":"Stern J, Jeanmonod D, Sarnthein J (2006) Persistent EEG overactivation in the cortical pain matrix of neurogenic pain patients. Neuroimage. https:\/\/doi.org\/10.1016\/j.neuroimage.2005.12.042","journal-title":"Neuroimage"},{"key":"4617_CR87","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.pain.2010.02.023","volume":"150","author":"KD Walton","year":"2010","unstructured":"Walton KD, Dubois M, Llin\u00e1s RR (2010) Abnormal thalamocortical activity in patients with complex regional pain syndrome (CRPS) type I. Pain 150:41\u201351","journal-title":"Pain"},{"key":"4617_CR88","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1007\/s10194-009-0140-4","volume":"10","author":"MH Bj\u00f8rk","year":"2009","unstructured":"Bj\u00f8rk MH, Stovner LJ, Engstr\u00f8m M, Stjern M, Hagen K, Sand T (2009) Interictal quantitative EEG in migraine: A blinded controlled study. J Headache Pain 10:331\u2013339","journal-title":"J Headache Pain"},{"key":"4617_CR89","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.ijpsycho.2011.03.013","volume":"80","author":"GG Knyazev","year":"2011","unstructured":"Knyazev GG (2011) Cross-frequency coupling of brain oscillations: an impact of state anxiety. Int J Psychophysiol 80:236\u2013245","journal-title":"Int J Psychophysiol"},{"key":"4617_CR90","doi-asserted-by":"publisher","first-page":"172192","DOI":"10.1155\/2015\/172192","volume":"2015","author":"C Styliadis","year":"2015","unstructured":"Styliadis C, Kartsidis P, Paraskevopoulos E, Ioannides AA, Bamidis PD (2015) Neuroplastic effects of combined computerized physical and cognitive training in elderly individuals at risk for dementia: an eLORETA controlled study on resting states. Neural Plast 2015:172192","journal-title":"Neural Plast"},{"key":"4617_CR91","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1016\/j.clinph.2014.07.027","volume":"126","author":"M Gram","year":"2015","unstructured":"Gram M, Graversen C, Olesen SS, Drewes AM (2015) Dynamic spectral indices of the electroencephalogram provide new insights into tonic pain. Clin Neurophysiol 126:763\u2013771","journal-title":"Clin Neurophysiol"},{"key":"4617_CR92","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1111\/j.1469-8986.2011.01329.x","volume":"49","author":"A Craig","year":"2012","unstructured":"Craig A, Tran Y, Wijesuriya N, Nguyen H (2012) Regional brain wave activity changes associated with fatigue. Psychophysiology 49:574\u2013582","journal-title":"Psychophysiology"}],"container-title":["Neurochemical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11064-025-04617-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11064-025-04617-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11064-025-04617-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T11:05:00Z","timestamp":1772622300000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11064-025-04617-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,11]]},"references-count":92,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["4617"],"URL":"https:\/\/doi.org\/10.1007\/s11064-025-04617-2","relation":{},"ISSN":["0364-3190","1573-6903"],"issn-type":[{"value":"0364-3190","type":"print"},{"value":"1573-6903","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,11]]},"assertion":[{"value":"1 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 November 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 November 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 December 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}},{"value":"As a corresponding author, I confirm that the manuscript has been read and approved for submission by all the named authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}}],"article-number":"13"}}