Institute of Biomaterials and Biomedical Engineering, Department of Electrical and Computer Engineering, University of Toronto
Lower urinary tract dysfunction is denoted by chronic symptoms – such as overactive bladder (OAB) – that can significantly affect the quality of life in millions of individuals worldwide. Although these symptoms can result directly from certain neurological disorders (e.g., spinal cord injury or multiple sclerosis), a far greater number of cases are attributed to idiopathic factors linked with advanced age.
Over the past decade, electrical neuromodulation technology has emerged as a widely-accepted alternative to pharmacological-based therapies for the treatment of OAB symptoms. Multi-center clinical trials have demonstrated the therapeutic efficacy of this approach (electrical stimulation of sacral (S3) nerve roots), but without any of the systemic side-effects that are common with drug therapies. The neural reflex pathways (“direct” bladder-inhibitory spinal reflex) have been fully characterized and the range of stimulation parameters for optimum therapeutic outcome are established. However, the need for constant electrical activation of this spinal reflex entails an invasive two-step surgical procedure for chronically implanting a nerve stimulation system, which consists of a nerve electrode, lead wires, and a pulse generator.
Work in our laboratory has focused on a markedly less-invasive approach to treating OAB. Referred to as posterior tibial nerve stimulation (PTNS) therapy, it involves a series of weekly out-patient nerve stimulation sessions (30-minutes of continuous nerve stimulation at 20 Hz) over a period of 3 months, at which point patients reach their therapeutic end-point. Although the efficacy of PTNS therapy has been confirmed through multi-center clinical trials, there is a paucity of data (both experimental and clinical) that can explain the neural mechanisms underlying this therapy. Consequently, there is very limited guidance for optimizing nerve stimulation for both achieving and maintaining the effects of PTNS therapy.
To this end, we have begun investigating the neurophysiological effects of PTNS in acute animal models of urinary function. Our recent studies indicate PTNS can elicit bladder-inhibitory reflexes within a broad range of stimulation frequencies (between 2 Hz and 50 Hz), and that these inhibitory effects can be maintained throughout the duration of PTN stimulation (e.g., 10 minute pulse train). Under certain stimulation conditions, bladder inhibition can persist beyond period of stimulation. Furthermore, we have shown that selective electrical stimulation of individual PTN branches (i.e., medial and lateral plantar nerves) can also elicit frequency-dependent reflexive inhibition of ongoing urinary activity.
Our early results provide evidence of multiple PTN sensory pathways that can be used to modulate independently bladder-inhibitory reflexes (e.g., transient vs. persistent inhibitory responses) in anesthetized animals. However, further work is needed to characterize the central mechanism of these pathways and thereby optimize the clinical use of this technology.