In spinal cord injury (SCI), onset of detrusor overactivity (DO) is detrimental for quality of life and renal function. Electrical neuromodulation implemented immediately after injury in patients after SCI is currently the only recognized way to prevent DO. As recently publish study analyzing urodynamics of spinal cord transected (SCT) rats has demonstrated that early administration of fesoterodine fumarate (FF) prevents the onset of DO , the aim of this experiment was to investigate whether the beneficial effect of FF was obtained by alternations in bladder muscarinic receptors.
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 from post-op day 1. After 6 weeks, animals were sacrificed. Bladders were assessed by hematoxylin/eosin and Masson’s trichrome staining to analyze variations of bladders layers. Immunofluorescence staining against muscarinic receptors (M1 to M5) was performed to investigate distribution of the receptors. Prevalence of the receptors was analyzed by Western blots. Comparisons were conducted using Kruskall-Wallis test (post-hoc Dunn test).
Morphological differences within bladder layers were not observed. Expression of M2 receptors was lower in all treated groups (Groups 3-6) when compared to SCT controls (Group 2) and statistical significance (p<0.05) was obtained in Groups 5 and 6 (Fig. 1). Expression of M3 receptors was higher in all treated groups (Groups 3-6) when compared to SCT controls (Group 2) and statistical significance (p<0.05) was obtained in Groups 4 and 5 (Fig. 1).
Early FF administration in a SCT rat model modifies profile of bladder muscarinic receptors. The treatment effect is sustained after the wash-out period. This is probably how early administration of anticholinergics prevents the onset of DO after SCT.
1. Biardeau X, et al. Early fesoterodine fumarate administration prevents neurogenic detrusor overactivity in a spinal cord transected rat model. PLoS One. 2017 Jan 6;12 (1):e0169694.