{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T04:21:53Z","timestamp":1791778913685,"version":"4.3.4"},"reference-count":116,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004622","name":"KWF Kankerbestrijding","doi-asserted-by":"publisher","award":["14719"],"award-info":[{"award-number":["14719"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Chronic pain is a major mental health burden with significant individual and societal impact. A major challenge in clinical practice is the considerable variability in treatment responses, reflecting the complexity of associated biopsychosocial factors and their neurobiological underpinnings. This narrative review presents an up\u2010to\u2010date overview of neural structures, circuits, and neurochemical systems involved in pain perception and modulation, integrating foundational and recent findings from human and animal studies. We outline current models of nociceptive processing and pain perception, emphasizing dynamic interactions between ascending nociceptive input, descending modulation, and distributed cortical networks. Additionally, we describe mechanisms at spinal, subcortical, and cortical levels, along with neuroplastic changes in chronic pain. Finally, we review key neuromodulators, including opioids, monoamines, cannabinoids, and GABA. Together, these insights support the development of personalized pain management strategies grounded in systems\u2010level neurobiology.<\/jats:p>","DOI":"10.1111\/ejn.70275","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T14:20:32Z","timestamp":1760710832000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Pain Perception and Modulation: Fundamental Neurobiology and Recent Advances"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9382-5130","authenticated-orcid":false,"given":"Willem\u00a0W.\u00a0J.","family":"van Strien","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Amsterdam UMC University of Amsterdam  Amsterdam the Netherlands"},{"name":"Department of Anesthesiology The Netherlands Cancer Institute\u2010Antoni van Leeuwenhoek Hospital  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8248-0244","authenticated-orcid":false,"given":"Markus\u00a0W.","family":"Hollmann","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Amsterdam UMC University of Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abo0689"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2020.108131"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.06.005"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001270"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nurt.2009.07.009"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002697"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X17666191001123900"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.10.037"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-022-00741-7"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2014.08.004"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.09.028"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000013253"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000008525"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-023-01455-9"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2016.68"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2016.05.033"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2020.04.029"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.14.7705"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25511"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2013.01.021"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/rapm-2020-101273"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.10.029"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04309-2"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1162-19.2019"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2020.07.004"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00393-7"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aap8586"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-080317-061522"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000003026"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhac332"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0284-z"},{"key":"e_1_2_11_33_1","first-page":"447","article-title":"The \u2018In's and Out's\u2019 of Descending Pain Modulation From the Rostral Ventromedial Medulla","volume":"47","author":"De Preter C. 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