Upregulation of LRRC8A in the anterior cingulate cortex mediates chronic visceral pain in adult male mice with neonatal maternal deprivation

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder primarily characterized by chronic visceral pain. Studies have reported that the anterior cingulate cortex (ACC) is involved in chronic visceral pain, however, the molecular mechanisms underlying this involvement remain largely unclear. In this study, we aimed to investigate the molecular mechanisms of the ACC in chronic visceral pain induced by neonatal maternal deprivation (NMD) in male mice. We showed that the expression of leucine-rich repeat-containing protein family member 8A (LRRC8A) at both mRNA and protein levels was significantly upregulated in the ACC of NMD male mice, with LRRC8A primarily co-localized in neurons. DCPIB, an inhibitor of LRRC8A, greatly alleviated chronic visceral pain. Moreover, the ATP concentration was significantly upregulated in the ACC of NMD male mice. However, LRRC8A was not involved in somatic pain induced by complete Freund's adjuvant (CFA) injection into the hind paw. In conclusion, our findings demonstrate that LRRC8A plays a critical role in regulating chronic visceral pain in NMD mice. These findings are expected to provide new ideas for the treatment of chronic visceral pain in IBS patients.