Medication Effects on Periurethral Sensation and Urethral Sphincter Activity

Abstract

Aim To characterize urethral neuromuscular function before and 2 weeks after medication therapy. Methods Premenopausal women without lower urinary tract symptoms were randomly allocated to one of six medications for 2 weeks (pseudoephedrine ER 120mg, imipramine 25mg, cyclobenzaprine 10mg, tamsulosin 0.4mg, solifenacin 5mg or placebo). At baseline and after medication, participants underwent testing: quantitative concentric needle EMG (CNE) of the urethral sphincter using automated Multi-Motor Unit Action Potential (MUP) software; current perception threshold (CPT) testing to measure periurethral sensation; and standard urodynamic pressure flow studies (PFS). Nonparametric tests were used to compare pre-post differences. Results 56 women had baseline testing; 48 (85.7%) completed follow-up CNE, and 49 (87.5%) completed follow-up CPT and PFS testing. Demographics showed no significant differences among medication groups with respect to age (mean 34.3 ± 10.1), BMI (mean 31.8 ± 7.5), parity (median 1, range 0–7), or race (14% Caucasian, 80% African American). PFS parameters were not significantly different within medication groups. No significant pre-post changes in CNE values were noted; however, trends in amplitudes were in a direction consistent with the expected physiologic effect of the medications. With CPT testing, a trend toward increased urethral sensation at the 5 Hz stimulation level, was observed following treatment with pseudoephedrine (0.15 to 0.09 mA at 5Hz; P=0.03). Conclusion In women without LUTS, pseudoephedrine improved urethral sensation, but not urethral neuromuscular function on CNE or pressure flow studies. Imipramine, cyclobenzaprine, tamsulosin, solifenacin, and placebo did not change urethral sensation or neuromuscular function.

Lower urinary tract electrical sensory assessment: a systematic review and meta‐analysis

“…Out of 80 studies, 61 exclusively applied CPTs [6,7,13–71], but four reported incomplete or no CPT results [14,32,61,64] (Table S2).…”

“…A trend towards increased sensation, i.e. decreased CPTs, was demonstrated after treatment with pseudoephedrine (only 5 Hz), while sensation was not changed by the other medications or placebo [42].…”

“…tolterodine, oxybutynin) in HS as well as in patients with idiopathic or neurogenic LUTD [38][39][40]. However, three other studies showed either unaltered or decreased CPTs after antimuscarinic treatment (solifenacin, tolterodine) in HS and non-neurogenic LUTD (urgency urinary incontinence) patients [41][42][43].…”

“…The skepticism is supported by a study lacking to demonstrate a significant difference in 5 Hz CPTs before and after resiniferatoxin instillation into the bladder [46], although resiniferatoxin should desensitize afferent C-fibres [46,97]. Furthermore, CPT studies persistently reported CPT values after 2000 Hz stimulation of the bladder mucosa, which would indicate the presence of A-beta fibres [16,19,20,27,31,35,39,42,43,47,48,65]. However, A-beta fibres have never been described in the LUT [3].…”

“…De Wachter (2001) [44] Mehnert (2007) [41] Vijaya (2012) [39] Greer (2015) [42] Eggersmann (1995) [55] Unclear risk radius of 10 mm [59]. This is important, as conditions in the LUT do not remain stable due to diuresis and consequently changes in bladder filling [90], which can affect electrode position, particularly in the bladder, and potentially also afferent activity, e.g.…”