{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T11:56:23Z","timestamp":1783857383833,"version":"3.55.0"},"reference-count":61,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,9,15]],"date-time":"2020-09-15T00:00:00Z","timestamp":1600128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81671093"],"award-info":[{"award-number":["81671093"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The occurrence of pain has always been closely related to a break in the balance between excitatory and inhibitory systems, and the internal relationship between these two systems has not been studied in the pathogenesis of chronic migraine (CM). In this study, we explored how inhibitory interneurons specifically modulate the glutamate\u2010induced hyperexcitability in the periaqueductal gray (PAG) of CM rats. The CM model was established by repeated dural infusion of inflammatory soup (IS) in rats. Then, Baclofen, a gamma\u2010aminobutyric acid type B receptor (GABABR) agonist; CGP35348, a GABABR antagonist; H89, a protein kinase A (PKA) inhibitor; and 8\u2010Bromo\u2010cAMP, a PKA agonist, were applied by intraventricular injection to investigate the detailed CM mechanism. Our results showed that GABABR2 mRNA and protein levels were significantly downregulated (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt;\u00a0.01) in the PAG of CM rats. Similarly, gamma\u2010aminobutyric acid (GABA) and its synthetase glutamate decarboxylase 65\/67 (GAD65\/67) seriously decreased (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt;\u00a0.01), implying a deficit in the function of inhibitory interneurons in the PAG of CM rats. Afterward, the application of Baclofen and H89 alleviated the IS\u2010evoked hyperalgesia and extenuated vesicular glutamate transporter 2 (VGLUT2), glutamate, calcitonin gene\u2010related peptide (CGRP), and c\u2010Fos expression by regulating the GABABR2\/PKA\/SynCAM1 pathway in the PAG of CM rats, while the application of CGP35348 and 8\u2010Bromo\u2010cAMP exactly exerted the opposite effect. Importantly, CGP35348 induced an elevation of CGRP, and VGLUT2 expression was relieved by H89. These data suggest that the loss in the function of inhibitory interneurons contributes to glutamate\u2010associated central sensitization through the GABABR2\/PKA\/SynCAM1 pathway in the PAG of CM rats.\n                  <\/jats:p>","DOI":"10.1096\/fj.202001561r","type":"journal-article","created":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T04:00:44Z","timestamp":1600747244000},"page":"14780-14798","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Deficiency in the function of inhibitory interneurons contributes to glutamate\u2010associated central sensitization through GABABR2\u2010SynCAM1 signaling in chronic migraine rats"],"prefix":"10.1096","volume":"34","author":[{"given":"Xiaoxu","family":"Zeng","sequence":"first","affiliation":[{"name":"Laboratory Research Center The First Affiliated Hospital of Chongqing Medical University Chongqing 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