Mechanisms resulting in abdominal pain include altered neuro-immune interactions in the gastrointestinal tract, but the signaling processes that link immune activation with visceral hypersensitivity are unresolved. We hypothesized that enteric glia link the neural and immune systems of the gut and that communication between enteric glia and immune cells modulates the development of visceral hypersensitivity. To this end, we manipulated a major mechanism of glial intercellular communication that requires connexin-43 and assessed the effects on acute and chronic inflammation, visceral hypersensitivity, and immune responses. Deleting connexin-43 in glia protected against the development of visceral hypersensitivity following chronic colitis. Mechanistically, the protective effects of glial manipulation were mediated by disrupting the glial-mediated activation of macrophages through the macrophage colony-stimulating factor. Collectively, our data identified enteric glia as a critical link between gastrointestinal neural and immune systems that could be harnessed by therapies to ameliorate abdominal pain.

导致腹痛的机制包括胃肠道中神经免疫相互作用的改变，但将免疫激活与内脏过敏联系起来的信号传导过程尚未解决。我们假设肠神经胶质细胞将肠道的神经系统和免疫系统联系起来，肠神经胶质细胞和免疫细胞之间的通讯调节内脏超敏反应的发展。为此，我们操纵了需要连接蛋白 43 的神经胶质细胞间通讯的主要机制，并评估了其对急性和慢性炎症、内脏超敏反应和免疫反应的影响。删除神经胶质细胞中的连接蛋白 43 可防止慢性结肠炎后内脏过敏的发生。从机制上讲，神经胶质操作的保护作用是通过巨噬细胞集落刺激因子破坏神经胶质介导的巨噬细胞激活来介导的。总的来说，我们的数据表明肠胶质细胞是胃肠神经和免疫系统之间的关键联系，可以通过治疗来缓解腹痛。