{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:16:17Z","timestamp":1785417377020,"version":"3.56.0"},"reference-count":66,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T00:00:00Z","timestamp":1780704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council","award":["113-2314-B-075A-007-MY3"],"award-info":[{"award-number":["113-2314-B-075A-007-MY3"]}]},{"award":["113-2314-B-075A-007-MY3"],"award-info":[{"award-number":["113-2314-B-075A-007-MY3"]}],"id":[{"id":"https:\/\/ror.org\/02kv4zf79","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010101","name":"Taichung Veteran General Hospital","doi-asserted-by":"publisher","award":["TCVGH-1143902C"],"award-info":[{"award-number":["TCVGH-1143902C"]}],"id":[{"id":"10.13039\/501100010101","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010101","name":"Taichung Veteran General Hospital","doi-asserted-by":"publisher","award":["TCVGH-NCHU1147623"],"award-info":[{"award-number":["TCVGH-NCHU1147623"]}],"id":[{"id":"10.13039\/501100010101","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010101","name":"Taichung Veteran General Hospital","doi-asserted-by":"publisher","award":["TCVGH-PU1148004"],"award-info":[{"award-number":["TCVGH-PU1148004"]}],"id":[{"id":"10.13039\/501100010101","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010101","name":"Taichung Veteran General Hospital","doi-asserted-by":"publisher","award":["TCVGH-1143907D"],"award-info":[{"award-number":["TCVGH-1143907D"]}],"id":[{"id":"10.13039\/501100010101","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010101","name":"Taichung Veteran General Hospital","doi-asserted-by":"publisher","award":["TCVGH-113G412"],"award-info":[{"award-number":["TCVGH-113G412"]}],"id":[{"id":"10.13039\/501100010101","id-type":"DOI","asserted-by":"publisher"}]},{"award":["TCVGH-1143902C"],"award-info":[{"award-number":["TCVGH-1143902C"]}],"id":[{"id":"https:\/\/ror.org\/00e87hq62","id-type":"ROR","asserted-by":"publisher"}]},{"award":["TCVGH-NCHU1147623"],"award-info":[{"award-number":["TCVGH-NCHU1147623"]}],"id":[{"id":"https:\/\/ror.org\/00e87hq62","id-type":"ROR","asserted-by":"publisher"}]},{"award":["TCVGH-PU1148004"],"award-info":[{"award-number":["TCVGH-PU1148004"]}],"id":[{"id":"https:\/\/ror.org\/00e87hq62","id-type":"ROR","asserted-by":"publisher"}]},{"award":["TCVGH-1143907D"],"award-info":[{"award-number":["TCVGH-1143907D"]}],"id":[{"id":"https:\/\/ror.org\/00e87hq62","id-type":"ROR","asserted-by":"publisher"}]},{"award":["TCVGH-113G412"],"award-info":[{"award-number":["TCVGH-113G412"]}],"id":[{"id":"https:\/\/ror.org\/00e87hq62","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neuropathic pain is a debilitating condition lacking objective and quantitative assessment tools, as current evaluations rely largely on subjective reports. Hyperspectral imaging (HSI) is a non-invasive technology that quantifies spatial and spectral tissue characteristics and has been applied in rheumatologic and metabolic disorders. This study investigated whether HSI-detected paw skin alterations correlate with graded nerve injury severity in a chronic constriction injury (CCI) model. Sprague\u2013Dawley rats were assigned to sham or CCI groups with one to four sciatic nerve ligatures. Behavioral assessments (CatWalk XT gait analysis, thermal hyperalgesia, and mechanical allodynia) and paw HSI measurements were performed longitudinally. Histological and molecular analyses were conducted from paw skin to dorsal spinal cord tissues. At 1100 nm, HSI demonstrated progressive and significant spectral deviations proportional to injury severity across all CCI groups, whereas 1300 nm changes were only detected in severe injuries. Histology revealed increased fibrosis, NGF, TNF-\u03b1, synaptophysin, and microglial activation with greater injury severity, alongside reduced PGP9.5, neurofilament, AChR, Desmin, GAP-43, Pax3, and BDNF expression. These molecular findings were supported by electrophysiological and behavioral impairments, which correlated with injury grade by HSI. In conclusion, HSI at 1100 nm provides a sensitive and objective indicator of neuropathic pain severity and holds promise as a quantitative translational tool.<\/jats:p>","DOI":"10.3390\/ijms27125164","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T05:43:46Z","timestamp":1780897426000},"page":"5164","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Validation of Paw Skin Hyperspectral Imaging for Assessing Neuropathic Pain Severity in a Chronic Constriction Injury Model"],"prefix":"10.3390","volume":"27","author":[{"given":"Hsin-Che","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Medical Research, Taichung Veterans General Hospital, Taichung 407219, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang-Yi","family":"Pan","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Science, National Chung-Hsing University, Taichung 407219, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Sheehan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Virginia, Charlottesville, VA 22903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0431-1282","authenticated-orcid":false,"given":"Meei-Ling","family":"Sheu","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Taichung Veterans General Hospital, Taichung 407219, Taiwan"},{"name":"Institute of Biomedical Science, National Chung-Hsing University, Taichung 407219, Taiwan"},{"name":"Rong Hsing Research Center for Translational Medicine, National Chung-Hsing University, Taichung 407219, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De-Wei","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Taichung Veterans General Hospital, Taichung 407219, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying Ju","family":"Chen","sequence":"additional","affiliation":[{"name":"PhD Program in Health and Social Welfare for Indigenous Peoples, Providence University, Taichung 407219, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Chia","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, National Central University, Taoyuan 407219, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong Lin","family":"Su","sequence":"additional","affiliation":[{"name":"Rong Hsing Research Center for Translational Medicine, National Chung-Hsing University, Taichung 407219, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsian-Min","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Taichung Veterans General Hospital, Taichung 407219, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3021-7676","authenticated-orcid":false,"given":"Hung-Chuan","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Taichung Veterans General Hospital, Taichung 407219, Taiwan"},{"name":"Rong Hsing Research Center for Translational Medicine, National Chung-Hsing University, Taichung 407219, Taiwan"},{"name":"Department of Neurosurgery, Neurological Institute, Taichung Veterans General Hospital, Taichung 407219, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"60","DOI":"10.18773\/austprescr.2018.022","article-title":"Neuropathic pain: Current definition and review of drug treatment","volume":"41","author":"Murnion","year":"2018","journal-title":"Aust. Prescr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1212\/01.wnl.0000282763.29778.59","article-title":"Neuropathic pain: Redefinition and a grading system for clinical and research purposes","volume":"70","author":"Treede","year":"2008","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1016\/j.pain.2011.06.017","article-title":"A new definition of neuropathic pain","volume":"152","author":"Jensen","year":"2011","journal-title":"Pain"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1155\/2014\/754693","article-title":"Pharmacological management of chronic neuropathic pain: Revised consensus statement from the Canadian Pain Society","volume":"19","author":"Moulin","year":"2014","journal-title":"Pain Res. Manag."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1001\/archneur.60.11.1524","article-title":"Advances in neuropathic pain: Diagnosis, mechanisms, and treatment recommendations","volume":"60","author":"Dworkin","year":"2003","journal-title":"Arch. Neurol."},{"key":"ref_6","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_7","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1474-4422(14)70251-0","article-title":"Pharmacotherapy for neuropathic pain in adults: A systematic review and meta-analysis","volume":"14","author":"Finnerup","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.pain.2004.12.010","article-title":"Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4)","volume":"114","author":"Bouhassira","year":"2005","journal-title":"Pain"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0304-3959(00)00482-6","article-title":"The LANSS Pain Scale: The Leeds assessment of neuropathic symptoms and signs","volume":"92","author":"Bennett","year":"2001","journal-title":"Pain"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1185\/030079906X132488","article-title":"painDETECT: A new screening questionnaire to identify neuropathic components in patients with back pain","volume":"22","author":"Freynhagen","year":"2006","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1111\/j.1468-1331.2010.02969.x","article-title":"EFNS guidelines on neuropathic pain assessment: Revised 2009","volume":"17","author":"Cruccu","year":"2010","journal-title":"Eur. J. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1016\/j.amjmed.2009.04.006","article-title":"Assessment of neuropathic pain in primary care","volume":"122","author":"Backonja","year":"2009","journal-title":"Am. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Leibovich, H., Buzaglo, N., Tsuriel, S., Peretz, L., Caspi, Y., Katz, B., Lev, S., Lichtstein, D., and Binshtok, A.M. (2020). Abnormal Reinnervation of Denervated Areas Following Nerve Injury Facilitates Neuropathic Pain. Cells, 9.","DOI":"10.3390\/cells9041007"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/1744-8069-8-61","article-title":"Spatiotemporal dynamics of re-innervation and hyperinnervation patterns by uninjured CGRP fibers in the rat foot sole epidermis after nerve injury","volume":"8","author":"Duraku","year":"2012","journal-title":"Mol. Pain"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.expneurol.2012.11.029","article-title":"Re-innervation patterns by peptidergic Substance-P, non-peptidergic P2X3, and myelinated NF-200 nerve fibers in epidermis and dermis of rats with neuropathic pain","volume":"241","author":"Duraku","year":"2013","journal-title":"Exp. Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Evans, L.J., Loescher, A.R., Boissonade, F.M., Whawell, S.A., Robinson, P.P., and Andrew, D. (2014). Temporal mismatch between pain behaviour, skin Nerve Growth factor and intra-epidermal nerve fibre density in trigeminal neuropathic pain. BMC Neurosci., 15.","DOI":"10.1186\/1471-2202-15-1"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1744-8069-8-1","article-title":"Neurotrophic factor changes in the rat thick skin following chronic constriction injury of the sciatic nerve","volume":"8","author":"Peleshok","year":"2012","journal-title":"Mol. Pain"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e33208","DOI":"10.1016\/j.heliyon.2024.e33208","article-title":"Hyperspectral imaging and its applications: A review","volume":"10","author":"Bhargava","year":"2024","journal-title":"Heliyon"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Selci, S. (2019). The Future of Hyperspectral Imaging. J. Imaging, 5.","DOI":"10.3390\/jimaging5110084"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.21037\/tcr.2019.12.53","article-title":"Applications of hyperspectral imaging in the detection and diagnosis of solid tumors","volume":"9","author":"Zhang","year":"2020","journal-title":"Transl. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1109\/10.7291","article-title":"Multispectral imaging of burn wounds: A new clinical instrument for evaluating burn depth","volume":"35","author":"Afromowitz","year":"1988","journal-title":"IEEE Trans. Biomed. Eng."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"046004","DOI":"10.1117\/1.JBO.20.4.046004","article-title":"Hyperspectral imaging-based wound analysis using mixture-tuned matched filtering classification method","volume":"20","author":"Calin","year":"2015","journal-title":"J. Biomed. Opt."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.burns.2014.05.002","article-title":"Characterization of burns using hyperspectral imaging technique\u2014A preliminary study","volume":"41","author":"Calin","year":"2015","journal-title":"Burns"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/wrr.12262","article-title":"Noninvasive imaging technologies for cutaneous wound assessment: A review","volume":"23","author":"Paul","year":"2015","journal-title":"Wound Repair Regen."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1021\/ac011275f","article-title":"Visible reflectance hyperspectral imaging: Characterization of a noninvasive, in vivo system for determining tissue perfusion","volume":"74","author":"Zuzak","year":"2002","journal-title":"Anal. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1177\/107385840100700105","article-title":"Neurotrophic factors: Important regulators of nociceptive function","volume":"7","author":"Bennett","year":"2001","journal-title":"Neuroscientist"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.neuron.2006.09.021","article-title":"Mechanisms of neuropathic pain","volume":"52","author":"Campbell","year":"2006","journal-title":"Neuron"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"250","DOI":"10.3171\/2013.9.JNS13353","article-title":"Comprehensive analysis of neurobehavior associated with histomorphological alterations in a chronic constrictive nerve injury model through use of the CatWalk XT system","volume":"120","author":"Chiang","year":"2014","journal-title":"J. Neurosurg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/0304-3959(92)90041-9","article-title":"An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat","volume":"50","year":"1992","journal-title":"Pain"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/0304-3959(90)91074-S","article-title":"A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury","volume":"43","author":"Seltzer","year":"1990","journal-title":"Pain"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e202400438","DOI":"10.1002\/jbio.202400438","article-title":"Optical Based Methods for Water Monitoring in Biological Tissue","volume":"18","author":"Perkov","year":"2025","journal-title":"J. Biophotonics"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Chiang, C.Y., Liu, S.A., Sheu, M.L., Chen, F.C., Chen, C.J., Su, H.L., and Pan, H.C. (2016). Feasibility of Human Amniotic Fluid Derived Stem Cells in Alleviation of Neuropathic Pain in Chronic Constrictive Injury Nerve Model. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0159482"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1007\/s11064-019-02850-0","article-title":"Experimental Characterization of the Chronic Constriction Injury-Induced Neuropathic Pain Model in Mice","volume":"44","author":"Gopalsamy","year":"2019","journal-title":"Neurochem. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"10901","DOI":"10.1117\/1.JBO.19.1.010901","article-title":"Medical hyperspectral imaging: A review","volume":"19","author":"Lu","year":"2014","journal-title":"J. Biomed. Opt."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e202300009","DOI":"10.1002\/jbio.202300009","article-title":"Hyperspectral imaging to accurately segment skin erythema and hyperpigmentation in cutaneous chronic graft-versus-host disease","volume":"16","author":"Saknite","year":"2023","journal-title":"J. Biophotonics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1177\/193229681000400508","article-title":"Hyperspectral imaging in diabetic foot wound care","volume":"4","author":"Yudovsky","year":"2010","journal-title":"J. Diabetes Sci. Technol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e202100220","DOI":"10.1002\/jbio.202100220","article-title":"Assessment of diabetic small-fiber neuropathy by using short-wave infrared hyperspectral imaging","volume":"15","author":"Sheen","year":"2022","journal-title":"J. Biophotonics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1080\/01431160600746456","article-title":"A survey of image classification methods and techniques for improving classification performance","volume":"28","author":"Lu","year":"2007","journal-title":"Int. J. Remote Sens."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1007\/s10916-019-1347-9","article-title":"Hyperspectral Image Features Classification Using Deep Learning Recurrent Neural Networks","volume":"43","author":"Venkatesan","year":"2019","journal-title":"J. Med. Syst."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1046\/j.1460-9568.1999.00590.x","article-title":"Neutralization of endogenous NGF prevents the sensitization of nociceptors supplying inflamed skin","volume":"11","author":"Koltzenburg","year":"1999","journal-title":"Eur. J. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Sheu, M.L., Chiang, C.Y., Su, H.L., Chen, C.J., Sheehan, J., and Pan, H.C. (2018). Intrathecal Injection of Dual Zipper Kinase shRNA Alleviating the Neuropathic Pain in a Chronic Constrictive Nerve Injury Model. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082421"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Su, H.L., Chiang, C.Y., Lu, Z.H., Cheng, F.C., Chen, C.J., Sheu, M.L., Sheehan, J., and Pan, H.C. (2018). Late administration of high-frequency electrical stimulation increases nerve regeneration without aggravating neuropathic pain in a nerve crush injury. BMC Neurosci., 19.","DOI":"10.1186\/s12868-018-0437-9"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1002\/glia.20871","article-title":"Microglia and neuropathic pain","volume":"57","author":"Inoue","year":"2009","journal-title":"Glia"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/glia.22379","article-title":"Microglia and intractable chronic pain","volume":"61","author":"Tsuda","year":"2013","journal-title":"Glia"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"104672","DOI":"10.1016\/j.neuint.2020.104672","article-title":"Chronic constriction injury of the sciatic nerve in rats causes different activation modes of microglia between the anterior and posterior horns of the spinal cord","volume":"134","author":"Nishihara","year":"2020","journal-title":"Neurochem. Int."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1093\/neuros\/nyw090","article-title":"Prevention of Axonal Degeneration by Perineurium Injection of Mitochondria in a Sciatic Nerve Crush Injury Model","volume":"80","author":"Kuo","year":"2017","journal-title":"Neurosurgery"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"E49","DOI":"10.1093\/neuros\/nyab105","article-title":"Dual Regeneration of Muscle and Nerve by Intramuscular Infusion of Mitochondria in a Nerve Crush Injury Model","volume":"89","author":"Sheu","year":"2021","journal-title":"Neurosurgery"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1006\/mcne.1999.0803","article-title":"Cooperation between HGF and CNTF in promoting the survival and growth of sensory and parasympathetic neurons","volume":"15","author":"Davey","year":"2000","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"8140","DOI":"10.1016\/S0021-9258(18)53072-6","article-title":"Enhancement of human hepatocyte growth factor production by interleukin-1 alpha, interleukin-1 beta, and tumor necrosis factor-alpha by fibroblasts in culture","volume":"268","author":"Tamura","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"588","DOI":"10.2183\/pjab.86.588","article-title":"The discovery of hepatocyte growth factor (HGF) and its significance for cell biology, life sciences and clinical medicine","volume":"86","author":"Nakamura","year":"2010","journal-title":"Proc. Jpn. Acad. Ser. B Phys. Biol. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"833","DOI":"10.5483\/BMBRep.2008.41.12.833","article-title":"The hepatocyte growth factor\/c-Met signaling pathway as a therapeutic target to inhibit angiogenesis","volume":"41","author":"You","year":"2008","journal-title":"BMB Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"30","DOI":"10.2353\/ajpath.2008.070583","article-title":"Hepatocyte growth factor exerts its anti-inflammatory action by disrupting nuclear factor-kappaB signaling","volume":"173","author":"Giannopoulou","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_53","first-page":"1163","article-title":"Multi-target anti-inflammatory action of hepatocyte growth factor","volume":"9","author":"Gong","year":"2008","journal-title":"Curr. Opin. Investig. Drugs"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.neuroscience.2004.06.031","article-title":"Hepatocyte growth factor as an enhancer of NMDA currents and synaptic plasticity in the hippocampus","volume":"128","author":"Akimoto","year":"2004","journal-title":"Neuroscience"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1634\/stemcells.2008-0226","article-title":"Endogenous hepatocyte growth factor is a niche signal for subventricular zone neural stem cell amplification and self-renewal","volume":"27","author":"Nicoleau","year":"2009","journal-title":"Stem Cells"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/0169-328X(95)00075-4","article-title":"Localization and functional coupling of HGF and c-Met\/HGF receptor in rat brain: Implication as neurotrophic factor","volume":"32","author":"Honda","year":"1995","journal-title":"Brain Res. Mol. Brain Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.1002\/jnr.21372","article-title":"Hepatocyte growth factor promotes endogenous repair and functional recovery after spinal cord injury","volume":"85","author":"Kitamura","year":"2007","journal-title":"J. Neurosci. Res."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Kitamura, K., Nagoshi, N., Tsuji, O., Matsumoto, M., Okano, H., and Nakamura, M. (2019). Application of hepatocyte growth factor for acute spinal cord injury: The road from basic studies to human treatment. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051054"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1080\/13543784.2024.2360191","article-title":"Clinical application and potential pluripotent effects of hepatocyte growth factor in spinal cord injury regeneration","volume":"33","author":"Hashimoto","year":"2024","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"5119","DOI":"10.1096\/fj.201800476R","article-title":"Effective control of neuropathic pain by transient expression of hepatocyte growth factor in a mouse chronic constriction injury model","volume":"32","author":"Nho","year":"2018","journal-title":"FASEB J."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Sheu, M.L., Pan, L.Y., Sheehan, J., Yang, M.Y., and Pan, H.C. (2022). Modulation of Aryl Hydrocarbon Receptor Expression Alleviated Neuropathic Pain in a Chronic Constriction Nerve Injury Animal Model. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911255"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"8261","DOI":"10.1007\/s12035-025-04786-9","article-title":"Caloric Restriction Attenuated Nerve Damages Mediated Through SIRT-1-a Study Using Nerve Crush Injury Model in Rats","volume":"62","author":"Sheu","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3917","DOI":"10.7150\/ijbs.105081","article-title":"Melatonin Ameliorate neuroinflammation in activated microglia through the Aryl hydrocarbon-Nrf2 axis","volume":"21","author":"Sheu","year":"2025","journal-title":"Int. J. Biol. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Sheu, M.-L., Pan, L.-Y., Yang, C.-N., Sheehan, J., Pan, L.-Y., You, W.-C., Wang, C.-C., Chen, H.-S., and Pan, H.-C. (2023). Neuronal Death Caused by HMGB1-Evoked via Inflammasomes from Thrombin-Activated Microglia Cells. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241612664"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Sheu, M.-L., Pan, L.-Y., Yang, C.-N., Sheehan, J., Pan, L.-Y., You, W.-C., Wang, C.-C., and Pan, H.-C. (2023). Thrombin-Induced Microglia Activation Modulated through Aryl Hydrocarbon Receptors. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241411416"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez-Morera, P., Casta\u00f1o-Gonz\u00e1lez, I., Travieso-Gonz\u00e1lez, C.M., Mompe\u00f3-Corredera, B., and Ortega-Santana, F. (2016). Quantification and statistical analysis methods for vessel wall components from stained images with Masson\u2019s trichrome. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0146954"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5164\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T04:17:04Z","timestamp":1781324224000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5164"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,6]]},"references-count":66,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27125164"],"URL":"https:\/\/doi.org\/10.3390\/ijms27125164","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,6]]}}}