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. 2017 Jan 6;12(1):e0169694.
doi: 10.1371/journal.pone.0169694. eCollection 2017.

Early Fesoterodine Fumarate Administration Prevents Neurogenic Detrusor Overactivity in a Spinal Cord Transected Rat Model

Xavier Biardeau  1 , Mikolaj Przydacz  1 , Shachar Aharony  1 , George Loutochin  1 , Lysanne Campeau  1 , Maeva Kyheng  2 , Jacques Corcos  1
Affiliations

Early Fesoterodine Fumarate Administration Prevents Neurogenic Detrusor Overactivity in a Spinal Cord Transected Rat Model

Xavier Biardeau et al. PLoS One. .

Abstract

Background: In spinal cord injury, onset of detrusor overactivity (DO) is detrimental for quality of life (incontinence) and renal risk. Prevention has only been achieved with complex sophisticated electrical neuromodulation techniques.

Purpose: To assess the efficacy of early fesoterodine fumarate (FF) administration in preventing bladder overactivity in a spinal cord transected (SCT) rat model.

Methods: 33 Sprague-Dawley rats were allocated to 6 groups-Group 1: 3 normal controls; Group 2: 6 SCT controls; Group 3: 6 SCT rats + FF 0.18 mg/kg/d; Group 4: 6 SCT rats + FF 0.12 mg/kg/d; Group 5: 6 SCT rats + FF 0.18 mg/kg/d + 72-h wash-out period; Group 6: 6 SCT rats + FF 0.12 mg/kg/d + 72-h wash-out period. SCT was performed at T10. FF was continuously administered. Cystometry was undertaken 6 weeks after SCT in awake rats recording intermicturition pressure (IMP), baseline pressure, threshold pressure (Pthres) and maximum pressure (Pmax). Normal controls and SCT controls were initially compared using the Mann-Whitney U tests in order to confirm the SCT effect on cystometric parameters. The comparisons in cystometric and metabolic cage parameters between SCT controls and treated rats were done using post-hoc Dunn's tests for Kruskal-Wallis analysis. Statistical testing was conducted at the two-tailed α-level of 0.05.

Results: Pressure parameters were significantly higher in SCT control group compared to normal controls. Six weeks after SCT, IMP was significantly lower in low dose treated group than in SCT controls. Pmax was significantly lower in 3 treated groups compared to SCT controls. Pthres was significantly lower in full time treated groups than in SCT controls.

Conclusion: Early administration of FF modulates bladder overactivity in a SCT rat model. Whereas short-term prevention has been demonstrated, the long-term should be further analyzed. Clinical application of these results should confirm this finding through randomized research protocols.

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Conflict of interest statement

Dr. Corcos reports other from Astellas, other from Pfizer, other from Allergan, during the conduct of the study. The Work Under Consideration for Publication: Astellas – adboard member; Pfizer – adboard member; Allergan – adboard member. Dr. Campeau reports other from Pfizer, during the conduct of the study. The Work Under Consideration for Publication: Pfizer - Consultant, Investigator initiated trial. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Study design.
Fig 2
Fig 2. Representative cystometries, time scales used are the same in all 6 groups of animals (Groups 1–6).
Control (Group 1): normal rats; SCT control (Group 2): untreated SCT rats; FF 0.18 (Group 3): SCT rats treated with FF 0.18 mg/kg/day; FF 0.12 (Group 4): SCT rats treated with FF 0.12 mg/kg/day; FF 0.18 + WOP (Group 5): SCT rats treated with FF 0.18 mg/kg/day + 72-h wash-out period; FF 0.12 + WOP (Group 6): SCT rats treated with FF 0.12 mg/kg/day + 72-h wash-out period; WOP: wash-out period.
Fig 3
Fig 3. Intermicturition pressure (Groups 2–6).
IMP: intermicturition pressure SCT control (Group 2): untreated SCT rats; FF 0.18 (Group 3): SCT rats treated with FF 0.18 mg/kg/day; FF 0.12 (Group 4): SCT rats treated with FF 0.12 mg/kg/day; FF 0.18 + WOP (Group 5): SCT rats treated with FF 0.18 mg/kg/day + 72-h wash-out period; FF 0.12 + WOP (Group 6): SCT rats treated with FF 0.12 mg/kg/day + 72-h wash-out period.
Fig 4
Fig 4. Maximum pressure (Groups 2–6).
Pmax: Maximum pressure SCT control (Group 2): untreated SCT rats; FF 0.18 (Group 3): SCT rats treated with FF 0.18 mg/kg/day; FF 0.12 (Group 4): SCT rats treated with FF 0.12 mg/kg/day; FF 0.18 + WOP (Group 5): SCT rats treated with FF 0.18 mg/kg/day + 72-h wash-out period; FF 0.12 + WOP (Group 6): SCT rats treated with FF 0.12 mg/kg/day + 72-h wash-out period.
Fig 5
Fig 5. Threshold pressure (Groups 1–6).
Pthres: Threshold pressure SCT control (Group 2): untreated SCT rats; FF 0.18 (Group 3): SCT rats treated with FF 0.18 mg/kg/day; FF 0.12 (Group 4): SCT rats treated with FF 0.12 mg/kg/day; FF 0.18 + WOP (Group 5): SCT rats treated with FF 0.18 mg/kg/day + 72-h wash-out period; FF 0.12 + WOP (Group 6): SCT rats treated with FF 0.12 mg/kg/day + 72-h wash-out period.
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