Anti-inflammatory effects of sacral nerve stimulation: a novel spinal afferent and vagal efferent pathway

Sacral nerve stimulation (SNS) was reported to improve 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. The aim of this study was to investigate whether the SNS anti-inflammatory effect is mediated via the local sacral splanchnic nerve or the spinal afferent-vagal efferent-colon pathway. Under general anesthesia, rats were administrated with TNBS intrarectally, and bipolar SNS electrodes were implanted unilaterally at S₃. The sacral and vagal nerves were severed at different locations for the assessment of the neural pathway. SNS for 10 days improved colonic inflammation only in groups with intact afferent sacral nerve and vagus efferent nerve. SNS markedly increased acetylcholine and anti-inflammatory cytokines (IL-10) and decreased myeloperoxidase and proinflammatory cytokines (IL-2, IL-17A, and TNF-α) in colon tissues. SNS increased the number of c-fos-positive cells in the brain stem and normalized vagal activity measured by spectral analysis of heart rate variability. SNS exerts an anti-inflammatory effect on TNBS-induced colitis by enhancing vagal activity mediated mainly via the spinal afferent-brain stem-vagal efferent-colon pathway.NEW & NOTEWORTHY Our findings support that there is a possible sacral afferent-vagal efferent pathway that can transmit sacral nerve stimulation to the colon tissue. Sacral nerve stimulation can be carried out by spinal cord afferent to the brain stem and then by the vagal nerve (efferent) to the target organ.