Effects of sacral neuromodulation on isolated urinary bladder function in a rat model of spinal cord injury.

Abstract

Sacral neuromodulation has been considered as an effective treatment option for various types of chronic voiding dysfunction, but the mechanism of action has not been well understood. The aim of this study was to evaluate the effect of chronic sacral neuromodulation on isolated bladder functions in a rat model of spinal cord injury. Female Sprague-Dawley rats (250-300 g; N = 20) were assigned to four groups as follows: 1) control group (N = 6); 2) spinal cord transection group (SCT; N = 5); 3) spinal cord transection + sacral neuromodulation group (SCT + SNM; N = 5); 4) sham (spinal cord transection + electrode wire implantation without sacral neuromodulation; N = 4). The rats in the SCT, SCT + SNM, and sham groups were anesthetized with ketamine (60 mg/kg, i.p.) and xylazine (7 mg/kg, i.p.). The spinal cord was completely transected at T8-T9 level in SCT and SCT + SNM groups. Electrode wires were implanted into S3 dorsal foramina in both sham and SNM groups, but only the SNM group was subjected to electrical stimulation for four hours a day for three weeks. Twenty-one days later, the rats were sacrificed via anesthetic overdose, and isolated longitudinal bladder strip preparations were placed in organ baths for the investigation of their isometric responses to pharmacological agents. In isometric contraction experiments, SCT was found to increase the contraction responses of the bladder strips to muscarinic stimulation, and SNM could not prevent this increase. In isometric relaxation experiments, SCT caused a decrease in β-adrenergic relaxation responses, and SNM augmented the bladder's β-adrenergic relaxation responses. Nitric oxide did not affect the relaxation responses. In our rat model of SCT, SNM seemed to alter adrenergic receptor function in the urinary bladder. Further studies are required to clarify the mechanism of these alterations at the level of bladder receptors following sacral neuromodulation.