Spinal stimulation of the upper lumbar spinal cord modulates urethral sphincter activity 1 in rats after spinal cord injury 2 Running head: Spinal stimulation modulates urethral sphincter activation

21 After spinal cord injury (SCI), the neurogenic bladder is observed to develop asynchronous 22 bladder and external urethral sphincter (EUS) contractions in a condition known as detrusor 23 sphincter dyssnergia (DSD). Activation of the EUS spinal controlling center located at upper 24 lumbar spinal cord may contribute to reduce EUS dyssynergic contractions and decrease urethral 25 resistance during voiding. However, this mechanism has not been well studied. This study aimed 26 at evaluating the effects of epidural stimulation (EpS) over the spinal EUS controlling center (L3) 27 in combination with a serotonergic receptor agonist on EUS relaxation in naive rats and chronic 28 (6-8 wk) T8 SCI rats. Cystometrogram and EUS electromyography (EMG) were obtained before 29 and after the intravenous administration of 5HT-1A receptors agonist and antagonist. The latency, 30 duration, frequency, amplitude, and area under curve of EpS-evoked EUS EMG responses were 31 analyzed. EpS on L3 evoked an inhibition of EUS tonic contraction and an excitation of EUS 32 intermittent bursting/relaxation correlating with urine expulsion in intact rats. Combined with a 33 5HT-1A receptor agonist, EpS on L3 evoked a similar effect in chronic T8 SCI rats to reduce 34 urethral contraction (resistance). This study examined the effect of facilitating the EUS spinal 35 controlling center to switch between urine storage and voiding phases by using EpS and a 36 serotonergic receptor agonist. This novel approach of applying EpS on the EUS controlling 37 center modulates EUS contraction and relaxation as well as reduces urethral resistance during 38 voiding in chronic SCI rats with DSD. 39 40