Dexmedetomidine alleviates chronic functional visceral pain in rats with irritable bowel syndrome through phosphorylation of ERK1 and CREB

Objective To investigate the protective effect of Dexmedetomidine (Dex) on the colon and spinal cord of irritable bowel syndrome (IBS) rats with chronic functional visceral pain, and its underlying mechanism of its effects on phosphorylation of extraeellular signal regulated kinase 1 (ERK1) and cyclic adenosine monophosphate response element binding protein (CREB). Methods Forty SPF-grade male SD rats (6~8 g) were inflicted with colorectal dilatation (CRD) stimulation to establish a rat model of irritable bowel syndrome (IBS). Then the animals were divided into normal group, model group, Dex group and Dex+pc group. The rats from the normal group do not do any treatment, and those of the model group, Dex group and Dex+pc group received CRD stimulation. After successful modeling, the rats in the Dex group were injected intraperitoneally with 5 μg/kg Dex hydrochloride injection daily, and those in the Dextpc group were injected intraperitoneally with 5 μg/kg Dex hydrochloride daily, as well as pc DNA3.1-CREB. The rats in the control group and model group were injected intraperitoneally with the same dose of normal saline and 100 nmol/L of pc DNA3.1-CREB-NC. TUNEL assay was used to detect cell apoptosis, real-time quantitative polymerase chain reaction (RT-qPCR) was employed to detect the mRNA expression of ERK1 and CREB, and Western blotting was used to detect the expression of p-ERK1 and p-CREB in rat spinal cord tissues. Results Compared with the normal group, the cell apoptotic rate, mRNA levels of ERK1 and CREB, and expression of p-ERK1 and p-CREB in spinal cord tissues were significantly increased in the model, Dex and Dex+pc groups (P < 0.05). The Dex group and Dex+pc group had obviously lower apoptotic rate, decreased ERK1 and CREB expression at mRNA level, and reduced expression of p-ERK1 and p-CREB than the model group (P < 0.05). What's more, apoptotic rate, mRNA expression of ERK1 and CREB, and protein expression of p-ERK1 and p-CREB were notably higher in the Dex+pc group than the Dex group (P < 0.05). Conclusion Dex can significantly inhibits the apoptosis in spinal cord tissue of rats with chronic functional visceral pain. It may play a protective role in colon and spinal cord tissues by inhibiting the phosphorylation of ERK1 and CREB.