{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T17:30:43Z","timestamp":1788629443476,"version":"build-2803163510"},"reference-count":149,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council","award":["NSTC 113-2314-B-030-007"],"award-info":[{"award-number":["NSTC 113-2314-B-030-007"]}]},{"name":"National Science and Technology Council","award":["NSTC 113-2515-S-030-001"],"award-info":[{"award-number":["NSTC 113-2515-S-030-001"]}]},{"name":"National Science and Technology Council","award":["NSTC 114-2918-I-030-001"],"award-info":[{"award-number":["NSTC 114-2918-I-030-001"]}]},{"name":"Teaching practice research program, Ministry of Education, Taiwan","award":["MOE-114-TPRGE-1002-030Y1"],"award-info":[{"award-number":["MOE-114-TPRGE-1002-030Y1"]}]},{"DOI":"10.13039\/501100013784","name":"Fu Jen Catholic University","doi-asserted-by":"crossref","award":["FJCU 114-A0114005"],"award-info":[{"award-number":["FJCU 114-A0114005"]}],"id":[{"id":"10.13039\/501100013784","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic pain is a pervasive and debilitating condition that affects millions of individuals worldwide. Unlike acute pain, which serves a protective physiological role, chronic pain persists beyond routine tissue healing and often arises without a discernible peripheral cause. Accumulating evidence indicates that chronic pain is not merely a symptom but a disorder of the central nervous system, underpinned by interacting molecular, neurochemical, and network-level alterations. Molecular neuroimaging using PET and MR spectroscopy has revealed dysregulated excitatory\u2013inhibitory balance (glutamate\/GABA), altered monoaminergic and opioidergic signaling, and neuroimmune activation (e.g., TSPO-indexed glial activation) in key pain-related regions such as the insula, anterior cingulate cortex, thalamus, and prefrontal cortex. Converging multimodal imaging\u2014including functional MRI, diffusion MRI, and EEG\/MEG\u2014demonstrates aberrant activity and connectivity across the default mode, salience, and sensorimotor networks, alongside structural remodeling in cortical and subcortical circuits. Parallel advances in neuromodulation, including transcranial magnetic stimulation (TMS), transcranial electrical stimulation (tES), deep brain stimulation (DBS), and emerging biomarker-guided closed-loop approaches, provide tools to perturb these maladaptive circuits and to test mechanistic hypotheses in vivo. This review integrates neuroimaging findings with molecular and systems-level mechanistic insights into chronic pain and its modulation, highlighting how imaging markers can link biochemical signatures to neural dynamics and guide precision pain management and individualized therapeutic strategies.<\/jats:p>","DOI":"10.3390\/ijms27021080","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T15:31:46Z","timestamp":1769009506000},"page":"1080","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Neuroimaging-Guided Insights into the Molecular and Network Mechanisms of Chronic Pain and Neuromodulation"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8322-1460","authenticated-orcid":false,"given":"Chiahui","family":"Yen","sequence":"first","affiliation":[{"name":"Department of International Business, Ming Chuan University, Taipei 111, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Chang","family":"Chiang","sequence":"additional","affiliation":[{"name":"Department of Life Science, College of Science and Engineering, Fu Jen Catholic University, New Taipei City 242, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","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":"ref_2","doi-asserted-by":"crossref","first-page":"106857","DOI":"10.1016\/j.nbd.2025.106857","article-title":"Role of efferocytosis in chronic pain\u2014From molecular perspective","volume":"207","author":"Zang","year":"2025","journal-title":"Neurobiol. 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