Multiple pudendal sensory pathways reflexly modulate bladder and urethral activity in patients with spinal cord injury

Abstract

Purpose: Electrical stimulation of pudendal afferents can evoke reflex bladder contractions with relaxation of the external urethral sphincter in cats. This voiding reflex is mediated by pudendal sensory fibers innervating the penile and prostatic urethra that engage spinal and spinobulbospinal micturition pathways, respectively. However, clinical translation of this potential therapy in individuals with spinal cord injury is limited by the lack of evidence showing analogous reflex mechanisms in humans. We investigated excitatory pudendal-to-bladder reflexes in 7 individuals with chronic spinal cord injury.

Materials and methods: We recorded isovolumetric bladder pressure and perineal electromyogram in response to intraurethral electrical stimulation at varying amplitudes and frequencies.

Results: Selective electrical stimulation of the proximal (29.7 ± 11.6 cm H(2)O) and distal urethral (23.3 ± 9.28 cm H(2)O) segments evoked sustained reflex bladder contractions in different subsets (3 each) of participants. In contrast, the corresponding reflex perineal electromyogram revealed a differential activation pattern between proximal and distal intraurethral stimulation (normalized electromyogram of 1.3 ± 0.2 and 0.3 ± 0.1, respectively, p <0.05).

Conclusions: To our knowledge we report the first clinical evidence of 2 independent excitatory pudendal-to-bladder reflex pathways, which in turn differentially modulate efferent pudendal output. Each reflex mechanism involves complex interaction of multiple sensory inputs and may provide a neural substrate to restore micturition after spinal cord injury.

Figure 1

A distension evoked bladder contraction during the initial urodynamic fill confirmed intact detrusor muscle and pelvic nerve function. The peak detrusor pressure, bladder pressure (not shown) minus the rectal pressure, was defined as maximum P_det. The recorded perineal electromyogram (raw EMG) was rectified and averaged to determine the maximum EMG activity evoked during a sustained bladder contraction. The bladder volume at which a sustained bladder contraction occurred was defined as the threshold (V_th).

Figure 2

Distension- and stimulation-evoked bladder contractions and perineal EMG activity in persons with spinal injury. (A) Robust distension-evoked bladder contractions were consistently accompanied by dyssynergic activity of the perineal musculature. (B) Proximal intraurethral (IU) stimulation (10 Hz, 4T, Exp 1) evoked sustained increases in detrusor pressure and high levels of perineal EMG activity that persisted throughout stimulation. (C) In contrast, electrical stimulation of the distal urethra (35 Hz, 2T, Exp 1) elicited a transient bladder contraction and low levels of perineal EMG.

Figure 3

Peak magnitude of bladder contractions evoked by proximal and distal intraurethral (IU) stimulation in persons with SCI. Electrical stimulation of the proximal urethra evoked sustained bladder contractions in 3 of 6 individuals with spinal cord injury. Stimulation of the distal urethra generated reflex bladder contractions in 3 of 6 participants. In both groups, the electrically evoked P_det were significantly greater than non-responses (*, p<0.05), but there was no difference between proximal and distal IU stimulation (p = 0.55).

Figure 4

The effect of stimulation (A) amplitude and (B) frequency on the normalized peak detrusor pressure (P_det). (A) Higher stimulus amplitudes applied to the proximal urethra resulted in significantly larger detrusor pressures (p < 0.05); whereas contractions evoked by stimulation of the distal urethra were not sensitive to the stimulus amplitude (p = 0.33). (B) Bladder contractions evoked by electrical stimulation of either the proximal (p = 0.43) or distal (p = 0.25) urethra were not dependent on stimulation frequency.

Figure 5

Electrical stimulation of the bladder neck in two participants that both exhibited distension evoked bladder contractions. Thirty-second trains of stimulation (frequency = 20 Hz, amplitude = T to 4T) failed to evoke directly sustained increases in bladder pressures that were comparable to distension evoked responses. The peak evoked detrusor pressures (P_det) in experiments 1 (T = 15 mA), and 4 (T = 20 mA), were 41 cmH₂O and 4 cmH₂O, respectively.

Figure 6

Reflex perineal EMG activity elicited by electrical stimulation of the proximal and distal urethra. The average normalized perineal EMG (norm EMG) evoked during bladder contractions generated by proximal IU stimulation (column 1, n = 3 participants) was significantly greater than the norm EMG measured both during distal IU stimulation evoked bladder contractions (column 4, n = 3 participants) and stimulation trials that failed to generate a bladder response (columns 2 and 3, “no response”). [*, p < 0.05; †, p < 0.001]

Figure 7

The effect of intraurethral (IU) stimulation amplitude and frequency on the normalized perineal EMG. The normalized perineal EMG evoked by proximal IU stimulation was dependent on the amplitude and frequency of stimulation (*, p < 0.05). In contrast, there was no significant effect of stimulation amplitude (p = 0.33) or frequency (p = 0.25) on the evoked reflex EMG activity during distal IU stimulation.