{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:54:28Z","timestamp":1791204868123,"version":"4.1.0"},"reference-count":69,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Veterinary Medicine &amp;amp; Sci"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Electroacupuncture (EA) is an important non\u2010pharmacological approach for pain management in veterinary and human medicine. However, electroacupuncture\u2010induced analgesic tolerance (EAT) limits its long\u2010term efficacy, and the underlying mechanisms remain unclear. Perilipin 4 (Plin4) is a lipid droplet\u2010associated protein involved in lipid storage, lipid droplet dynamics, and cellular lipid homeostasis. Emerging evidence suggests that it also plays a role in neuronal lipid metabolic changes and pain modulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate the role of Plin4 in the development of EAT and explore its potential as a molecular target for attenuating this limitation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>EAT was induced in male mice by daily 100\u00a0Hz EA stimulation for 7 consecutive days. Plin4 expression levels in the amygdala, periaqueductal grey, and spinal cord were examined, and immunofluorescence was used to determine cellular localization. The functional role of Plin4 was assessed by intrathecal Plin4 knockdown in mice and by Plin4 overexpression or knockdown in N2a cells. A total of 99 male mice were used in the primary experiments, with an additional 24 mice used for siRNA knockdown validation in the Supporting Information.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Repeated EA induced analgesic tolerance and markedly upregulated Plin4 in the spinal cord, amygdala, and periaqueductal grey. In the spinal cord, increased Plin4 was mainly localized to spinal cord dorsal horn neurons. Intrathecal Plin4 knockdown delayed EAT onset and increased the pain threshold. In N2a cells, Plin4 expression was positively associated with lipid droplet formation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Spinal neuronal Plin4 contributes to the development of EA\u2010induced analgesic tolerance, possibly by altering neuronal lipid homeostasis. Plin4 may represent a potential molecular target for attenuating tolerance, prolonging EA\u2010induced analgesia, and optimizing EA\u2010based pain management strategies in veterinary medicine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/vms3.71220","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:53:03Z","timestamp":1789519983000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular and Immunohistochemical Analyses of PLIN4 in the Spinal Cord and Brain During the Development of Electroacupuncture\u2010Induced Analgesic Tolerance in Mice"],"prefix":"10.1002","volume":"12","author":[{"given":"Shao\u2010Jia","family":"Jiang","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine Huazhong Agricultural University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4021-8692","authenticated-orcid":false,"given":"Shi\u2010Ya","family":"Cao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Huazhong Agricultural University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming\u2010Fei","family":"Fan","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Huazhong Agricultural University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Huazhong Agricultural University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui\u2010Ling","family":"Yin","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Huazhong Agricultural University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang\u2010Hui","family":"Lei","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Huazhong Agricultural University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sha","family":"Nan","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Huazhong Agricultural University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao\u2010Long","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Huazhong Agricultural University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi\u2010Hui","family":"Cai","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Huazhong Agricultural University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u2010Ya","family":"Jiao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Huazhong Agricultural University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Huang","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory for Biomedical Photonics Wuhan National Laboratory for Optoelectronics Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3968-8490","authenticated-orcid":false,"given":"Yi","family":"Ding","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Huazhong Agricultural University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5076-308X","authenticated-orcid":false,"given":"Xiao\u2010Shu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chinese Medicine Resource and Compound Prescription Ministry of Education Hubei University of Chinese Medicine  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin\u2010Yue","family":"Chai","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Huazhong Agricultural University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"American Veterinary Medical Association (AVMA).2020.AVMA Guidelines for the Euthanasia of Animals: 2020 Edition. 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