Zainab Moazzam1, Austin R Duke2, Paul B Yoo3. 1. Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada. 2. Nuviant Medical, Inc., Dallas, Texas. 3. Department of Electrical and Computer Engineering, University of Toronto, Toronto, Ontario, Canada. Electronic address: paul.yoo@utoronto.ca.
Abstract
PURPOSE: Tibial nerve stimulation is a minimally invasive neuromodulation treatment of overactive bladder. However, in addition to our limited understanding of the underlying mechanisms, there are also questions regarding the long-term delivery of tibial nerve stimulation therapy in patients. We aimed to characterize the effects of stimulation frequency using a wirelessly powered implantable stimulation device. METHODS AND MATERIALS: Six α-chloralose anesthetized adult male cats were used in this study. A multicontact lead was surgically implanted subcutaneously in the hind limb and used to stimulate the tibial nerve. Using an isovolumetric bladder a short duration of electrical pulses was applied at amplitudes 3 times the motor threshold and at frequencies from 2 to 20 Hz. RESULTS: Implant driven stimulation of the tibial nerve resulted in frequency dependent activation of bladder reflexes. Low frequency tibial nerve stimulation (2 Hz) consistently evoked excitatory responses (mean ± SE 32.9% ± 3.8%). In contrast, higher frequency tibial nerve stimulation (6 to 20 Hz) inhibited bladder function (overall mean 14.9% ± 2.4%). Although low foot motor thresholds were achieved at initial implantation (mean 0.83 ± 0.05 mA), a notable elevation in threshold amplitude was observed 5 hours after implantation. CONCLUSIONS: To our knowledge this study provides the first evidence of frequency dependent modulation of bladder function in anesthetized cats. The inhibitory influence of tibial nerve stimulation at frequencies above 6 Hz transitioned to an excitatory effect at 2 Hz. Taken together these preclinical data support the feasibility of using a wirelessly powered implantable device to potentially modulate bladder function in patients.
PURPOSE: Tibial nerve stimulation is a minimally invasive neuromodulation treatment of overactive bladder. However, in addition to our limited understanding of the underlying mechanisms, there are also questions regarding the long-term delivery of tibial nerve stimulation therapy in patients. We aimed to characterize the effects of stimulation frequency using a wirelessly powered implantable stimulation device. METHODS AND MATERIALS: Six α-chloralose anesthetized adult male cats were used in this study. A multicontact lead was surgically implanted subcutaneously in the hind limb and used to stimulate the tibial nerve. Using an isovolumetric bladder a short duration of electrical pulses was applied at amplitudes 3 times the motor threshold and at frequencies from 2 to 20 Hz. RESULTS: Implant driven stimulation of the tibial nerve resulted in frequency dependent activation of bladder reflexes. Low frequency tibial nerve stimulation (2 Hz) consistently evoked excitatory responses (mean ± SE 32.9% ± 3.8%). In contrast, higher frequency tibial nerve stimulation (6 to 20 Hz) inhibited bladder function (overall mean 14.9% ± 2.4%). Although low foot motor thresholds were achieved at initial implantation (mean 0.83 ± 0.05 mA), a notable elevation in threshold amplitude was observed 5 hours after implantation. CONCLUSIONS: To our knowledge this study provides the first evidence of frequency dependent modulation of bladder function in anesthetized cats. The inhibitory influence of tibial nerve stimulation at frequencies above 6 Hz transitioned to an excitatory effect at 2 Hz. Taken together these preclinical data support the feasibility of using a wirelessly powered implantable device to potentially modulate bladder function in patients.
Authors: Shun Li; Xing Li; Katherine Theisen; Jeffery Browning; Bing Shen; Jicheng Wang; James R Roppolo; William C de Groat; Changfeng Tai Journal: Am J Physiol Renal Physiol Date: 2017-10-25
Authors: Jiajie Jessica Xu; Lauren L Zimmerman; Vanessa H Soriano; Georgios Mentzelopoulos; Eric Kennedy; Elizabeth C Bottorff; Chris Stephan; Kenneth Kozloff; Maureen J Devlin; Tim M Bruns Journal: Int Urogynecol J Date: 2022-03-07 Impact factor: 2.894
Authors: Katherine Theisen; Jeffery Browning; Xing Li; Shun Li; Bing Shen; Jicheng Wang; James R Roppolo; William C de Groat; Changfeng Tai Journal: Neuromodulation Date: 2018-06-27