title: Spinal stimulation of the upper lumbar spinal cord modulates urethral sphincter activity in rats after spinal cord injury.
abstract: After spinal cord injury (SCI), the neurogenic bladder is observed to develop asynchronous bladder and external urethral sphincter (EUS) contractions in a condition known as detrusor-sphincter dyssnergia (DSD). Activation of the EUS spinal controlling center located at the upper lumbar spinal cord may contribute to reduce EUS dyssynergic contractions and decrease urethral resistance during voiding. However, this mechanism has not been well studied. This study aimed at evaluating the effects of epidural stimulation (EpS) over the spinal EUS controlling center (L3) in combination with a serotonergic receptor agonist on EUS relaxation in naive rats and chronic (6-8 wk) T8 SCI rats. Cystometrogram and EUS electromyography (EMG) were obtained before and after the intravenous administration of 5HT-1A receptor agonist and antagonist. The latency, duration, frequency, amplitude, and area under curve of EpS-evoked EUS EMG responses were analyzed. EpS on L3 evoked an inhibition of EUS tonic contraction and an excitation of EUS intermittent bursting/relaxation correlating with urine expulsion in intact rats. Combined with a 5HT-1A receptor agonist, EpS on L3 evoked a similar effect in chronic T8 SCI rats to reduce urethral contraction (resistance). This study examined the effect of facilitating the EUS spinal controlling center to switch between urine storage and voiding phases by using EpS and a serotonergic receptor agonist. This novel approach of applying EpS on the EUS controlling center modulates EUS contraction and relaxation as well as reduces urethral resistance during voiding in chronic SCI rats with DSD.
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, California;
authors.forename: Edsel M
authors.initials: EM
authors.lastname: Abud
authors.affiliation: School of Biomedical Sciences, University of Leeds, Leeds, United Kingdom.
authors.forename: Ronaldo M
authors.initials: RM
authors.lastname: Ichiyama
authors.affiliation: Department of Anesthesiology and Perioperative Care, University of California, Irvine, California; Department of Anatomy and Neurobiology, University of California, Irvine, California; Department of Neurology, University of California, Irvine, California; Reeve-Irvine Research Center, University of California, Irvine, California; Department of Neurology, University of California, Los Angeles, California; and.
authors.forename: Leif A
authors.initials: LA
authors.lastname: Havton
authors.affiliation: Department of Anesthesiology and Perioperative Care, University of California, Irvine, California; Department of Neurology, University of California, Los Angeles, California; and HuiyiHarriet.Chang@med.usc.edu.
authors.forename: Huiyi H
authors.initials: HH
authors.lastname: Chang
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004599:Electric Stimulation Therapy / Q000379:methods*; D004576:Electromyography; D005260:Female; D008159:Lumbar Vertebrae; D017207:Rats, Sprague-Dawley; D012018:Reflex; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology; D013116:Spinal Cord / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000150:complications* / Q000503:physiopathology; D013997:Time Factors; D014521:Urethra / Q000187:drug effects / Q000294:innervation*; D001750:Urinary Bladder, Neurogenic / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D014563:Urodynamics / Q000187:drug effects
chemical_list: D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists
keywords: electromyography; epidural stimulation; serotonergic receptors; urethral resistance