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To date, effective therapies for pain have remained limited. Although multiple factors have been reported to modulate pain, few studies have explored the neural mechanisms of long non-coding RNA in pain.<\/jats:p>\n                  <jats:p>Here, we identified a high expression level of Carip in the lateral parabrachial nucleus (LPBN), which participates in modulating pain-like behaviours. Thermal stimulation can induce the significant upregulation of long non-coding RNA Carip in LPBN neurons. The knockout of Carip elevates pain thresholds. Electrophysiological assays in the LPBN\u2013central nucleus of the amygdala (CeA) neurocircuit demonstrated that Carip knockout simultaneously increased the amplitude of evoked AMPA receptor excitatory postsynaptic currents and evoked GABAA receptor inhibitory postsynaptic currents, disrupting the neuronal excitation and inhibition balance due to the enhanced phosphorylation of synapsin 1 Ser9 via a protein kinase A-dependent signalling cascade in LPBN neurons, which is determined to be the crucial reason for abnormal pain-like behaviours.<\/jats:p>\n                  <jats:p>Importantly, blocking the Carip-mediated intracellular signalling cascade by specific knockdown of synapsin 1 or protein kinase A in LPBN neurons of Carip knockout mice not only restores the excitation\/inhibition balance but also ameliorates abnormal pain-like behaviours.<\/jats:p>\n                  <jats:p>Together, our results demonstrate the important roles of Carip in pain-like behaviours and suggest that modulating excitation\/inhibition balance via the Carip-mediated intracellular signalling pathway could effectively alleviate pain. Our study provides synaptic and molecular explanations for how Carip modulates pain-like behaviours.<\/jats:p>","DOI":"10.1093\/brain\/awag073","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T12:43:09Z","timestamp":1771591389000},"page":"3599-3613","source":"Crossref","is-referenced-by-count":0,"title":["Long non-coding RNA\n                    <i>Carip<\/i>\n                    loss alters parabrachial synapses and drives pain hyposensitivity"],"prefix":"10.1093","volume":"149","author":[{"given":"Feng","family":"Xu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cognitive Science and Mental Health, State Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences , Beijing 100101 ,","place":["China"]},{"name":"Sino-Danish Center for Education and Research, Sino-Danish College, College of Life Sciences, University of Chinese Academy of Sciences , Beijing 100049 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