title: Caveolin-1 in the anterior cingulate cortex modulates chronic neuropathic pain via regulation of NMDA receptor 2B subunit.
abstract: Chronic pain is still a basic science and clinical challenge. Unraveling of the neurobiological mechanisms involved in chronic pain will offer novel targets for the development of therapeutic strategies. It is well known that central sensitization in the anterior cingulate cortex (ACC) plays a critical role in initiation, development, and maintenance of chronic pain. However, the underlying mechanisms still remain elusive. Here, we reported that caveolin-1 (Cav-1), a scaffolding protein in membrane rafts, was persistently upregulated and activated in the ACC neurons after chronic constriction injury (CCI) in mice. Knockdown or blocking of Cav-1 in the contralateral ACC to the injury side reversed CCI-induced pain behavioral and neuronal sensitization and overexpression of Cav-1 in the ipsilateral ACC-induced pain behavior in the unaffected hindpaw. Furthermore, we found that Cav-1 directly binding with NMDA receptor 2B subunit (NR2B) and promotion of NR2B surface levels in the ACC contributed to modulation of chronic neuropathic pain. Disrupting the interaction of Cav-1 and NR2B through microinjection of a short peptide derived from the C-terminal of NR2B into the ACC exhibited a significant anti-nociception effect associated with decrease of surface NR2B expression. Moreover, Cav-1 increased intracellular Ca(2+) concentration and activated the ERK/CREB signaling pathway in an NR2B-dependent manner in the ACC. Our findings implicate that Cav-1 in the ACC neurons modulates chronic neuropathic pain via regulation of NR2B and subsequent activation of ERK/CREB signaling, suggesting a possible caveolin-mediated process would participate in neuronal transmission pathways implicated in pain modulation.
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, China, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, China, and.
authors.forename: Jun-Xia
authors.initials: JX
authors.lastname: Yang
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, China, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, China, and.
authors.forename: Lu
authors.identifier: http://orcid.org/0000-0003-3347-3819
authors.initials: L
authors.lastname: Hua
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, China, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, China, and.
authors.forename: Yan-Qiang
authors.initials: YQ
authors.lastname: Li
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, China, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, China, and.
authors.forename: Yan-Yu
authors.initials: YY
authors.lastname: Jiang
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, China, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, China, and.
authors.forename: Dong
authors.initials: D
authors.lastname: Han
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, China, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, China, and.
authors.forename: He
authors.initials: H
authors.lastname: Liu
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, China, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, China, and.
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Tang
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, China, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, China, and.
authors.forename: Xiao-Na
authors.initials: XN
authors.lastname: Yang
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, China, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, China, and.
authors.forename: Cui
authors.initials: C
authors.lastname: Yin
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, China, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, China, and.
authors.forename: Ling-Yun
authors.initials: LY
authors.lastname: Hao
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, China, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, China, and.
authors.forename: Le
authors.initials: L
authors.lastname: Yu
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, China, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, China, and.
authors.forename: Peng
authors.initials: P
authors.lastname: Wu
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, China, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, China, and.
authors.forename: Cui-Jie
authors.initials: CJ
authors.lastname: Shao
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, China, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, China, and.
authors.forename: Hai-Lei
authors.initials: HL
authors.lastname: Ding
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, China, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, China, and.
authors.forename: Yong-Mei
authors.initials: YM
authors.lastname: Zhang
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, China, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, China, and Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China caojl03100@yahoo.com.
authors.forename: Jun-Li
authors.initials: JL
authors.lastname: Cao
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000502:physiology*; D059350:Chronic Pain / Q000378:metabolism* / Q000473:pathology; D055785:Gene Knockdown Techniques; D006179:Gyrus Cinguli / Q000378:metabolism* / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D009437:Neuralgia / Q000378:metabolism* / Q000473:pathology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
chemical_list: D051242:Caveolin 1; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate
keywords: NMDA receptor 2B subunit; anterior cingulate cortex; caveolin-1; neuropathic pain