To explore the mechanism of action of sacral nerve stimulation (SNS) in the treatment of slow transit constipation (STC) by observing its effect on the expression of 5-hydroxytryptamine 4 receptor (5-HT₄R) in the colonic tissue of STC mice.

Thirty Kunming mice were randomly divided into normal and modeling groups, with 10 mice in the normal group and 20 mice in the modeling group. The modeling group was gavaged with compound difenocoumarol suspension, and the normal group was fed normally. After the success of the STC mouse model, the modeling group was then divided into the SNS group and the model group. The SNS group received sacral nerve stimulation therapy; the normal group and the model group were subjected to daily acupuncture at the skin site corresponding to the S3 nerve foramen, with a 2-week treatment duration for all groups. After treatment, the fecal moisture content, intestinal propulsion rate, expression of 5-HT₄R protein, 5-HT₄R mRNA expression levels, and c-kit immunohistochemistry in the colon were measured in each group.

Compared with the normal group, the model group showed significantly reduced fecal moisture content (t=22.43, P<0.05) and intestinal propulsion rate (t=12.67, P<0.05), as well as significantly decreased expression of 5-HT₄R protein (t=5.96, P<0.05), 5-HT₄R mRNA (t=9.92, P<0.05), and c-kit protein immunohistochemistry in the colonic tissue (t=5.44, P<0.05). Compared with the model group, the SNS group exhibited significantly increased fecal moisture content (t=19.36, P<0.05) and intestinal propulsion rate (t=7.47, P<0.05), along with significantly increased expression of 5-HT₄R protein (t=4.76, P<0.05), 5-HT₄R mRNA (t=13.74, P<0.05), and c-kit protein immunohistochemistry in the colonic tissue (t=5.39, P<0.05).

Sacral nerve stimulation may alleviate constipation symptoms in STC mice, potentially associated with the upregulation of 5-HT₄R and c-kit expression in colonic tissues, which may promote the proliferation of interstitial cells of Cajal, enhance their cellular function, and ultimately improve intestinal motility.