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Sensory pudendal nerve stimulation increases bladder capacity through sympathetic mechanisms in cyclophosphamide‐induced cystitis rats
Author(s) -
Gonzalez Eric J.,
Grill Warren M.
Publication year - 2019
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.23860
Subject(s) - medicine , pudendal nerve , stimulation , interstitial cystitis , overactive bladder , neuromodulation , cystometry , urology , urinary bladder , anesthesia , sensory nerve , sensory system , urinary system , pathology , neuroscience , alternative medicine , biology
Aims Interstitial cystitis and bladder pain syndrome is a prevalent health concern with inadequate treatments. Neuromodulation has emerged as a therapeutic option to treat patients refractory to standard care. The objective of this study was to determine the efficacy and mechanism(s) of sensory pudendal nerve stimulation on bladder function in cystitis rats. Methods Female rats were administered saline ( n = 8) or cyclophosphamide (CYP, 150 mg/kg IP, n = 16) and single‐trial cystometry experiments were conducted under urethane anesthesia 48 h after injection. Electrical stimulation (0.02‐0.22 mA, 10‐20 Hz) was delivered to the sensory branch of the pudendal nerve and its effect on the bladder and external urethral sphincter were measured. Stimulation trials were also conducted following bilateral hypogastric nerve transection (HGNT) or pharmacological inhibition of beta‐adrenergic receptors (propranolol, 1 mg/kg IV) to determine the mechanisms of bladder inhibition. Results CYP‐induced cystitis decreased bladder capacity ( P = 0.0352) and bladder compliance ( P = 0.024) by up to 38% of control. Electrical stimulation of the sensory pudendal nerve increased bladder capacity ( P < 0.0001) in control and CYP rats by up to 51‐52% of their respective baselines. HGNT did not influence bladder inhibition generated by sensory pudendal nerve stimulation in control rats, whereas HGNT and propranolol decreased the efficacy of electrical stimulation in CYP rats. Conclusions Sympathetic reflex activity mediates sensory pudendal nerve stimulation in CYP treated but not control rats. These studies demonstrate an alternative approach to neuromodulation in cystitis and establish mechanistic changes during stimulation that may enable the development of novel therapeutics.