Vol. 300, Issue 2, 421-427, February 2002

Altered Glutamate Receptor Function during Recovery of Bladder Detrusor-External Urethral Sphincter Coordination in a Rat Model of Spinal Cord Injury

Victor Pikov and Jean R. Wrathall

Department of Neuroscience, Georgetown University, Washington, DC

Coordination of the bladder detrusor and the external urethral sphincter is a supraspinally controlled reflex that is essential for efficient micturition. This coordination is permanently lost after spinal cord transection but can recover chronically after incomplete spinal cord injury (SCI). As glutamatergic transmission plays a key role in all levels of detrusor-external urethral sphincter coordination, we examined the role of potential alterations in glutamatergic control in its recovery after SCI. Rats were subjected to standardized incomplete contusion injury. Detrusor-external urethral sphincter coordination was evaluated urodynamically at 5 days (subacute) and 8 weeks (chronic) after SCI. Sensitivity of coordinated activation of the external urethral sphincter in response to bladder distension to the  -amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid/kainate antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo(f)quinoxaline-7-sulfonamide disodium (NBQX) and to the N-methyl-D-aspartate (NMDA) antagonist R(-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP) was determined by intrathecal application at the L6 spinal cord level during urodynamic recordings. We found that while detrusor contractions recovered at 5 days after SCI, coordinated activation of the external urethral sphincter was significantly impaired at 5 days and recovered only by 8 weeks. There was no difference in sensitivity of detrusor-external urethral sphincter coordination to NBQX at the subacute or chronic time points. However, external urethral sphincter response to bladder distension was sensitive to a 50% lower dose of CPP at 5 days compared with uninjured rats or chronic recovered SCI rats. Thus, alterations in NMDA receptor function appeared to be involved in recovery of detrusor-external urethral sphincter coordination after incomplete SCI.