{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T03:33:47Z","timestamp":1790134427855,"version":"4.0.1"},"reference-count":82,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T00:00:00Z","timestamp":1623283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>This study aimed to investigate the regulation of pain hypersensitivity induced by the spinal synaptic transmission mechanisms underlying interleukin (IL)\u201010 and glucagon\u2010like peptide 1 receptor (GLP\u20101R) agonist exenatide\u2010induced pain anti\u2010hypersensitivity in neuropathic rats through spinal nerve ligations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Neuropathic pain model was established by spinal nerve ligation of L5\/L6 and verified by electrophysiological recording and immunofluorescence staining. Microglial expression of \u03b2\u2010endorphin through autocrine IL\u201010\u2010 and exenatide\u2010induced inhibition of glutamatergic transmission were performed by behavioral tests coupled with whole\u2010cell recording of miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) through application of endogenous and exogenous IL\u201010 and \u03b2\u2010endorphin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Intrathecal injections of IL\u201010, exenatide, and the \u03bc\u2010opioid receptor (MOR) agonists \u03b2\u2010endorphin and DAMGO inhibited thermal hyperalgesia and mechanical allodynia in neuropathic rats. Whole\u2010cell recordings of bath application of exenatide, IL\u201010, and \u03b2\u2010endorphin showed similarly suppressed enhanced frequency and amplitude of the mEPSCs in the spinal dorsal horn neurons of laminae II, but did not reduce the frequency and amplitude of mIPSCs in neuropathic rats. The inhibitory effects of IL\u201010 and exenatide on pain hypersensitive behaviors and spinal synaptic plasticity were totally blocked by pretreatment of IL\u201010 antibody, \u03b2\u2010endorphin antiserum, and MOR antagonist CTAP. In addition, the microglial metabolic inhibitor minocycline blocked the inhibitory effects of IL\u201010 and exenatide but not \u03b2\u2010endorphin on spinal synaptic plasticity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This suggests that spinal microglial expression of \u03b2\u2010endorphin mediates IL\u201010\u2010 and exenatide\u2010induced inhibition of glutamatergic transmission and pain hypersensitivity via presynaptic and postsynaptic MORs in spinal dorsal horn.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.13694","type":"journal-article","created":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T05:43:39Z","timestamp":1623390219000},"page":"1157-1172","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Spinal microglial \u03b2\u2010endorphin signaling mediates IL\u201010 and exenatide\u2010induced inhibition of synaptic plasticity in neuropathic 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