C‐Fos expression in the spinal cord after acute sacral segmental nerve stimulation

Abstract

Sacral nerve stimulation (SNS) can provide subjective and objective relief of pelvic pain and chronic voiding symptoms, but its mechanism is poorly understood. It is well known that a noxious stimulus applied to one part of the body can reduce the response to a subsequent stimulus elsewhere in the body. This phenomenon, known as diffuse noxious inhibitory controls (DNIC), seems to be the mechanism by which pain can be reduced by concurrent noxious stimulation. On the basis of the DNIC concept, we investigated the expression of a protein product of proto-oncogene c-Fos (c-Fos) in the rat spinal cord after acute electrical stimulation of the sacral segmental nerve with or without lower urinary tract irritation. Adult male Sprague-Dawley rats were treated either by sacral nerve stimulation (SNS) from the S1 sacral foramen or chemical irritation of the lower urinary tract (LUT) or both. Rats were perfused transcardially, and spinal cords were removed and processed for c-Fos immunohistochemistry. c-Fos expression in the central nervous system was detected by immunohistochemistry by using the avidin-biotin technique. The number of c-Fos-positive cells and their locations in the spinal cord were evaluated. SNS and LUT irritation resulted in significant increases in c-Fos-positive cells in L6 and S1 spinal segments. In the animals treated by SNS and LUT irritation, counts of c-Fos-positive cells in L6 and S1 segments were significantly smaller than expected. Distribution and number of c-Fos-positive cells in rats that received SNS and LUT irritation were almost the same as those induced by SNS alone in the S1 segment. SNS alone caused a near maximal response in c-Fos expression such that adding LUT irritation did not cause a linear increase in c-Fos. Subsequent LUT irritation could not induce additional expression of c-Fos within the spinal cord.