Mapping and neuromodulation of lower urinary tract function using spinal cord stimulation in female rats

Abstract

Spinal cord epidural stimulation (SCS) represents a form of neuromodulation for the management of spasticity and pain. This technology has recently emerged as a new approach for potentially augmenting locomotion and voiding function in humans and rodents after spinal cord injury. However, the effect of SCS on micturition has not been studied extensively. Here, SCS was first applied as a direct stimulus onto individual segmental levels of the lumbar spinal cord in rats to map evoked external urethral sphincter (EUS) electromyography activity and SCS-induced voiding contractions. SCS of L2-3 inhibited EUS tonic activity, and SCS on L3 (L3/SCS) inhibited EUS tonic activity and elicited EUS bursting. In contrast, SCS of L1 and L4-6 evoked EUS tonic contractions, which resembled the urethral guarding reflex during bladder storage. Next, the effects of a bilateral pelvic nerve crush (PNC) injury on urodynamic function were examined at 14 days post-operatively. The PNC injury resulted in decreased voiding efficiency and maximum intravesical pressure, whereas the post-voiding residual volume was increased, suggestive of an underactive bladder. Finally, L3/SCS was performed to induce a voiding contraction and enable voiding in rats with a PNC injury. Voiding efficiency was significantly increased, and the residual volume was decreased by L3/SCS in rats after the PNC injury. We conclude that L3/SCS may be used to induce micturition reflexes in a partially filled bladder, reduce urethral resistance, and augment bladder emptying after PNC injury.

Keywords: Electromyography; External urethral sphincter; Pelvic nerve; Underactive bladder.

Figure 1

Mapping of the external urethral sphincter (EUS) spinal relaxation center. SCS was applied on the first lumbar spinal segment (L1) through the sixth lumbar spinal segment (L6) in rats (n=7). The bladder was filled at 50-80% of voiding capacity. SCS on L2 evoked inhibition of EUS tonic activity compared to the baseline without SCS in the same animal. SCS on L3 evoked not only inhibition of EUS tonic activity but also EUS bursting without bladder contraction. SCS applied to L1, L4-L6 elicited EUS tonic activity. The black thick bars indicate the duration of SCS. Asterisks indicate the non-voiding contractions during SCS.

Figure 2

Urodynamic recordings and morphological bladder and urethral changes in control and PNC rats. Note that voiding contractions are associated with coordinated EUS EMG activity in both the control and PNC injury series (A, B). The PNC injury resulted in decreased amplitude of voiding contractions (B). The bladder wall thickness measurements showed a statistical trend for a possible increase (unpaired t-test, p=0.06; n=6) after the PNC injury (C), whereas the urethral thickness was significantly increased (unpaired t-test, p=0.04; n=6) after the PNC injury (D).

Figure 3

L3/SCS evoked voiding contractions in control and PNC rats. The control rat (A) received 55% of the bladder capacity by saline infusion at the rate of 0.1 mL/min. After stopping saline infusion, L3/SCS (40 Hz, 0.2 ms pulse width, 3.2 volts) was given for 82 s. The evoked voiding contractions happened at the latency of 48 s after the end of stimulation. The EUS EMG activity was suppressed before reaching the voiding threshold. In the PNC rat (B), the infusion volume was 72% of the bladder capacity. L3/SCS (40 Hz, 0.2 ms pulse width, 2.8 volts) was given for 84 s. The evoked voiding contractions happened at the latency of 60 s after the end of stimulation. The EUS EMG activity was suppressed during L3/SCS. The black thick bars indicate the duration of L3/SCS. Arrows indicate when the voiding occurred.