{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:03:19Z","timestamp":1791892999756,"version":"4.3.4"},"reference-count":39,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"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":["Brain and Behavior"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Neuropathic pain is sustained by maladaptive synaptic plasticity in the spinal dorsal horn. Increasing evidence suggests that metabolic regulation is closely linked to synaptic function, as lipid metabolism, membrane microdomain organization, NAD\n                      <jats:sup>+<\/jats:sup>\n                      \u2010dependent signaling, and cellular stress\u2010response pathways can influence receptor trafficking, neuronal excitability, and activity\u2010dependent synaptic remodeling. Because cannabinoid CB1 receptor (CB1R) signaling participates in both pain processing and metabolic control, we investigated whether CB1R modulation is associated with coordinated changes in spinal synaptic plasticity and metabolic regulators.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A chronic constriction injury (CCI) mouse model was used. Mice were treated with the CB1R antagonist AM251 or the CB1R agonist WIN55,212\u20102. Mechanical and thermal hypersensitivity, C\u2010fiber\u2013evoked long\u2010term potentiation in the spinal dorsal horn, plasma lipid indices, and the expression of CB1R, SREBP1, NAMPT, and SIRT1 were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CB1R activation alleviated CCI\u2010induced mechanical and thermal hypersensitivity and attenuated exaggerated C\u2010fiber\u2013evoked spinal long\u2010term potentiation, whereas CB1R inhibition produced the opposite tendency. AM251 reduced spinal dorsal horn CB1R, SREBP1, and NAMPT protein levels by 49.0%, 37.8%, and 57.5%, respectively, compared with untreated CCI mice, while increasing SIRT1 protein by 17.8% (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.01). In contrast, WIN55,212\u20102 increased CB1R, SREBP1, and NAMPT protein levels by 24.5%, 23.7%, and 17.2%, respectively, and reduced SIRT1 protein by 28.8% compared with untreated CCI mice (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.01). qPCR analysis showed consistent changes at the transcriptional level.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CB1R activation is associated with pain relief, suppression of spinal synaptic potentiation, and coordinated regulation of the SREBP1\/NAMPT\/SIRT1 metabolic axis. These findings suggest that CB1R\u2010mediated metabolic regulation may contribute to maladaptive spinal synaptic plasticity in neuropathic pain.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71837","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T11:31:46Z","timestamp":1791891106000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cannabinoid CB1 Receptor Regulates Spinal Dorsal Horn Synaptic Plasticity in a Mouse Model of Neuropathic Pain through the CB1R\/SREBP1\/NAMPT\/SIRT1 Metabolic Regulatory Framework"],"prefix":"10.1002","volume":"16","author":[{"given":"Lu","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Wuhan Children's Hospital  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenglong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pain Wuhan Fourth Hospital  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Wuhan Children's Hospital  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Wuhan Children's Hospital  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Wuhan Children's Hospital  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Wuhan Children's Hospital  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"issue":"9","key":"e_1_2_12_2_1","article-title":"Cannabinoid Receptors and Their Relationship With Chronic Pain: A Narrative Review","volume":"12","author":"Anthony A. 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