{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T05:48:14Z","timestamp":1781070494266,"version":"3.54.1"},"reference-count":42,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T00:00:00Z","timestamp":1686787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Harbin Medical University","award":["31021220003"],"award-info":[{"award-number":["31021220003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Patients with vascular dementia experience more pain than healthy elders, potentially due to the presence of central neuropathic pain. However, the mechanisms underlying neuropathic pain in vascular dementia remain poorly understood, and there is currently a lack of effective treatment available. In this study, a rat model of vascular dementia was induced by permanently occluding the common carotid arteries bilaterally (2-VO). The cognitive impairments in the 2-VO rats were evaluated using the Morris Water Maze test, while HE and LBF staining were employed to assess brain tissue lesions in the hippocampal, cerebral cortex, and white matter regions known to be associated with severe memory and learning deficits. Furthermore, pain-related behavioral tests, including mechanical and thermal stimuli assessments, were conducted, and in vivo electrophysiological recordings of primary sensory neurons were performed. Compared to sham-operated and pre-operative rats, rats with vascular dementia exhibited mechanical allodynia and thermal hyperalgesia 30 days after surgery. Furthermore, in vivo electrophysiology revealed a significant increase in the occurrence of spontaneous activity of A\u03b2- and C-fiber sensory neurons in the rat model of vascular dementia. These results indicate that neuropathic pain behaviors developed in the rat model of vascular dementia, and abnormal spontaneous discharges of primary sensory neurons may play a crucial role in the development of pain after vascular dementia.<\/jats:p>","DOI":"10.3390\/ijms241210198","type":"journal-article","created":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T01:31:31Z","timestamp":1686879091000},"page":"10198","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Abnormal Spontaneous Discharges of Primary Sensory Neurons and Pain Behavior in a Rat Model of Vascular Dementia"],"prefix":"10.3390","volume":"24","author":[{"given":"Xiaodan","family":"Song","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Analysis and Analytical Chemistry, College of Pharmacy, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4136-0462","authenticated-orcid":false,"given":"Yingji","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Inorganic Chemistry and Physics Chemistry, College of Pharmacy, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9221-7167","authenticated-orcid":false,"given":"Chunjuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis and Analytical Chemistry, College of Pharmacy, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"},{"name":"Department of Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.4068\/cmj.2011.47.2.66","article-title":"Vascular dementia","volume":"47","author":"Lee","year":"2011","journal-title":"Chonnam Med. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1016\/S0140-6736(15)00463-8","article-title":"Vascular dementia","volume":"386","author":"Thomas","year":"2015","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1093\/pm\/pnab327","article-title":"A Cross-Sectional Study of Pain Sensitivity and Unpleasantness in People with Vascular Dementia","volume":"23","author":"Beach","year":"2022","journal-title":"Pain Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e803","DOI":"10.1097\/PR9.0000000000000803","article-title":"Pain in dementia","volume":"5","author":"Achterberg","year":"2020","journal-title":"Pain Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"471","DOI":"10.2174\/1567205013666160602234109","article-title":"Pain Experience in Dementia Subtypes: A Systematic Review","volume":"14","author":"Binnekade","year":"2017","journal-title":"Curr. Alzheimer Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1111\/pme.12637","article-title":"Chronic pain in \u201cprobable\u201d vascular dementia: Preliminary findings","volume":"16","author":"Scherder","year":"2015","journal-title":"Pain Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1007\/s40266-012-0001-8","article-title":"Assessment and management of pain, with particular emphasis on central neuropathic pain, in moderate to severe dementia","volume":"29","author":"Scherder","year":"2012","journal-title":"Drugs Aging"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/S1474-4422(09)70176-0","article-title":"Central post-stroke pain: Clinical characteristics, pathophysiology, and management","volume":"8","author":"Klit","year":"2009","journal-title":"Lancet Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/S1474-4422(02)00190-4","article-title":"Subcortical ischaemic vascular dementia","volume":"1","author":"Roman","year":"2002","journal-title":"Lancet Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S48","DOI":"10.1161\/STROKEAHA.108.537704","article-title":"Understanding white matter disease: Imaging-pathological correlations in vascular cognitive impairment","volume":"40","author":"Black","year":"2009","journal-title":"Stroke"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/j.exger.2012.05.023","article-title":"Vascular dementia: Different forms of vessel disorders contribute to the development of dementia in the elderly brain","volume":"47","author":"Thal","year":"2012","journal-title":"Exp. Gerontol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"45","DOI":"10.2165\/11630070-000000000-00000","article-title":"Pain mechanisms in patients with chronic pain","volume":"32","author":"Fornasari","year":"2012","journal-title":"Clin. Drug Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1111\/jphp.12007","article-title":"Establishment of a central post-stroke pain model using global cerebral ischaemic mice","volume":"65","author":"Tamiya","year":"2013","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1111\/j.2042-7158.2010.01231.x","article-title":"Abeta and Adelta but not C-fibres are involved in stroke related pain and allodynia: An experimental study in mice","volume":"63","author":"Takami","year":"2011","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.neuroscience.2013.01.005","article-title":"Involvement of LPA1 receptor signaling in cerebral ischemia-induced neuropathic pain","volume":"235","author":"Halder","year":"2013","journal-title":"Neuroscience"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S0006-8993(01)03223-1","article-title":"Axonal damage and demyelination in the white matter after chronic cerebral hypoperfusion in the rat","volume":"924","author":"Wakita","year":"2002","journal-title":"Brain Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.brainresrev.2007.01.003","article-title":"Permanent, bilateral common carotid artery occlusion in the rat: A model for chronic cerebral hypoperfusion-related neurodegenerative diseases","volume":"54","author":"Farkas","year":"2007","journal-title":"Brain Res. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1111\/j.1471-4159.2010.06958.x","article-title":"Experimental models of vascular dementia and vascular cognitive impairment: A systematic review","volume":"115","author":"Jiwa","year":"2010","journal-title":"J. Neurochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1012.e25","DOI":"10.1016\/j.neurobiolaging.2011.10.033","article-title":"Selective white matter abnormalities in a novel rat model of vascular dementia","volume":"33","author":"Kitamura","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref_20","unstructured":"Paxinos, G., and Watson, C. (2007). The Rat Brain in Stereotaxic Coordinates, Elsevier Academic Press Inc.. [6th ed.]."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.2147\/CIA.S36739","article-title":"Pain management in patients with dementia","volume":"8","author":"Achterberg","year":"2013","journal-title":"Clin Interv Aging."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1016\/j.pain.2012.04.019","article-title":"Partial nerve injury induces electrophysiological changes in conducting (uninjured) nociceptive and nonnociceptive DRG neurons: Possible relationships to aspects of peripheral neuropathic pain and paresthesias","volume":"153","author":"Djouhri","year":"2012","journal-title":"Pain"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Washida, K., Hattori, Y., and Ihara, M. (2019). Animal Models of Chronic Cerebral Hypoperfusion: From Mouse to Primate. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20246176"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1007\/s007020100019","article-title":"Chronic cerebral hypoperfusion in the rat enhances age-related deficits in spatial memory","volume":"108","author":"Sopala","year":"2001","journal-title":"J. Neural Transm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.jneumeth.2010.06.010","article-title":"In vivo visualization and functional characterization of primary somatic neurons","volume":"191","author":"Ma","year":"2010","journal-title":"J. Neurosci. Methods"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7651","DOI":"10.1038\/s41598-019-44172-9","article-title":"Adjacent intact nociceptive neurons drive the acute outburst of pain following peripheral axotomy","volume":"9","author":"Chen","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1124\/jpet.106.103614","article-title":"Inhibition of paclitaxel-induced A-fiber hypersensitization by gabapentin","volume":"318","author":"Matsumoto","year":"2006","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1254\/jphs.11102FP","article-title":"Spinal mechanism underlying the antiallodynic effect of gabapentin studied in the mouse spinal nerve ligation model","volume":"118","author":"Morimoto","year":"2012","journal-title":"J. Pharmacol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.brainres.2006.01.088","article-title":"Neuroprotection by cilostazol, a phosphodiesterase type 3 inhibitor, against apoptotic white matter changes in rat after chronic cerebral hypoperfusion","volume":"1082","author":"Lee","year":"2006","journal-title":"Brain Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1523\/JNEUROSCI.23-07-02517.2003","article-title":"Tumor necrosis factor-alpha induces mechanical allodynia after spinal nerve ligation by activation of p38 MAPK in primary sensory neurons","volume":"23","author":"Schafers","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.pain.2010.02.025","article-title":"Macrophage inflammatory protein-1alpha mediates the development of neuropathic pain following peripheral nerve injury through interleukin-1beta up-regulation","volume":"149","author":"Kiguchi","year":"2010","journal-title":"Pain"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5249","DOI":"10.1523\/JNEUROSCI.0802-07.2007","article-title":"Contribution of downregulation of L-type calcium currents to delayed neuronal death in rat hippocampus after global cerebral ischemia and reperfusion","volume":"27","author":"Li","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.pathophys.2007.09.009","article-title":"Disruption of ionic and cell volume homeostasis in cerebral ischemia: The perfect storm","volume":"14","author":"Mongin","year":"2007","journal-title":"Pathophysiology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1744-8069-2-33","article-title":"Nerve injury induces robust allodynia and ectopic discharges in Nav1.3 null mutant mice","volume":"2","author":"Nassar","year":"2006","journal-title":"Mol. Pain"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0169-328X(01)00188-7","article-title":"Dorsal root ganglion neurons show increased expression of the calcium channel alpha2delta-1 subunit following partial sciatic nerve injury","volume":"95","author":"Newton","year":"2001","journal-title":"Brain Res. Mol. Brain Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.neuron.2015.06.005","article-title":"Nociception, Pain, Negative Moods, and Behavior Selection","volume":"87","author":"Baliki","year":"2015","journal-title":"Neuron"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.ejphar.2012.01.025","article-title":"Chrysin improves cognitive deficits and brain damage induced by chronic cerebral hypoperfusion in rats","volume":"680","author":"He","year":"2012","journal-title":"Eur. J. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1089\/jmf.2009.1242","article-title":"Water extract of Triticum aestivum L. and its components demonstrate protective effect in a model of vascular dementia","volume":"13","author":"Han","year":"2010","journal-title":"J. Med. Food"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0165-0270(84)90007-4","article-title":"Developments of a water-maze procedure for studying spatial learning in the rat","volume":"11","author":"Morris","year":"1984","journal-title":"J. Neurosci. Methods"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1097\/00005072-195312040-00008","article-title":"A method for the combined staining of cells and fibers in the nervous system","volume":"12","author":"Kluver","year":"1953","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/0304-3959(88)90026-7","article-title":"A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia","volume":"32","author":"Hargreaves","year":"1988","journal-title":"Pain"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2098","DOI":"10.1152\/jn.00748.2005","article-title":"Inflammatory mediators enhance the excitability of chronically compressed dorsal root ganglion neurons","volume":"95","author":"Ma","year":"2006","journal-title":"J. Neurophysiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/12\/10198\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:56:00Z","timestamp":1760126160000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/12\/10198"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,15]]},"references-count":42,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["ijms241210198"],"URL":"https:\/\/doi.org\/10.3390\/ijms241210198","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,15]]}}}