NEUROMODULATION REDUCES C-FOS GENE EXPRESSION IN SPINALIZED RATS: A DOUBLE-BLIND RANDOMIZED STUDY

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Abstract
Purpose: Neuromodulation of the sacral nerve roots is effective to treat various voiding dysfunctions, but the underlying mechanism of neuromodulation is not known. The objective of this study is to evaluate whether inhibition of afferent c-fiber activity is the underlying mechanism of sacral nerve root neuromodulation. Materials and Methods: Twenty-nine female Sprague-Dawley rats weighing 220 to 250 gm. were divided into 4 groups: normal control (normal rats without any procedure; n = 5), sham with saline (spinalized rats at T9 with saline bladder instillation; n = 7), sham with acetic acid (spinalized rats at T9 with acetic acid bladder instillation; n = 8) and stimulation group (spinalized rats at T9 with acetic acid bladder instillation plus electrical stimulation; n = 9). A cystometrogram was performed 10 days after spinal cord transection to confirm the development of bladder hyperreflexia. Bilateral electrode wires were implanted into S1 dorsal foramina and electrical stimulation was performed 8 hours a day for three weeks. The rats were perfused with 4% paraformaldehyde and an immunocytochemical method was used to stain fos-protein that was encoded by c-fos gene. A double-blind method was used in counting fos-protein positive neurons. Results: Bladder hyperreflexia developed in all spinalized rats 10 days after spinal cord transection. Peak bladder pressure was found significantly reduced after neuromodulation (30.4 ± 4.2 cm. water) compared with the same rats before neuromodulation (82.4 ± 10.2 cm. water; p = 0.007). The number of fos-protein positive neurons in the L6 spinal cord segment in the neuromodulation group (93.2 ± 13.3 cells/section) decreased significantly when compared with the sham with acetic acid group (160.6 ± 25.0 cells/section; p = 0.02). There was no significant difference in c-fos expression between the sham with saline group (90.5 ± 15.6 cells/section) and the neuromodulation group (p = 0.92). Conclusions: Sacral dorsal root neuromodulation reduces c-fos gene expression and bladder hyperreflexia in spinalized rats, through inhibition of afferent c-fiber activity.