Rab27a-mediated exosome secretion in anterior cingulate cortex contributes to colorectal visceral pain in adult mice with neonatal maternal deprivation

Aims: Chronic visceral pain is a common symptom of irritable bowel syndrome (IBS). Exosomes are involved in the development of pain. Rab27a can mediate the release of exosomes. The purpose of this study is to investigate how Rab27a-mediated exosome secretion in anterior cingulate cortex (ACC) regulates visceral hyperalgesia induced with neonatal maternal deprivation (NMD) in adult mice. Methods: The colorectal distension (CRD) method was adopted to measure visceral pain. The BCA protein assay kit was applied to detect the exosomes' protein concentration. Western blotting, Q-PCR and immunofluorescence technique were adopted to detect the expression of Rab27a and the markers of exosomes. Results: Exosomes extracted from ACC were more in NMD mice than in CON mice. Injection of exosome specific inhibitor GW4869 in ACC attenuated colorectal visceral pain of NMD mice. Injection of NMD-derived exosomes produced colorectal visceral pain in CON mice. Rab27a was upregulated in ACC of NMD mice. Rab27a was highly expressed in ACC neurons of NMD mice, rather than astrocytes and microglia. Injection of Rab27a-siRNA reduced the release of exosomes and attenuated the colorectal visceral pain in NMD mice. Conclusions: This study suggested that overexpression of Rab27a increased exosome secretion in ACC neurons, thus contributing to visceral hyperalgesia in NMD mice. Keywords: Irritable bowel syndrome; Visceral pain; Anterior cingulate cortex; Exosome; Rab27a

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