The long-lasting post-stimulation inhibitory effects of bladder activity induced by posterior tibial nerve stimulation in unanesthetized rats

Abstract

Tibial nerve stimulation (TNS) is one of the neuromodulation methods used to treat an overactive bladder (OAB). However, the treatment mechanism is not accurately understood owing to significant differences in the results obtained from animal and clinical studies. Thus, this study was aimed to confirm the response of bladder activity to the different stimulation frequencies and to observe the duration of prolonged post-stimulation inhibitory effects following TNS. This study used unanesthetized rats to provide a closer approximation of the clinical setting and evaluated the changes in bladder activity in response to 30 min of TNS at different frequencies. Moreover, we observed the long-term changes of post-stimulation inhibitory effects. Our results showed that bladder response was immediately inhibited after 30 min of 10 Hz TNS, whereas it was excited at 50 Hz TNS. We also used the implantable stimulator to observe a change in duration of the prolonged post-stimulation inhibitory effects of the TNS and found large discrepancies in the time that the inhibitory effect lasted after stimulation between individual animals. This study provides important evidence that can be used to understand the neurophysiological mechanisms underlying the bladder inhibitory response induced by TNS as well as the long-lasting prolonged post-stimulation effect.

Posterior Tibial Nerve Stimulation for Overactive Bladder: Mechanism, Classification, and Management Outlines

“…However, the therapy appears to modify spinal cord reflexes and brain involvement via afferent signals rather than direct motor stimulation of the detrusor or urethral sphincter. According to the most widely recognized explanation, neuromodulations interrupt or interfere with the afferent nerve input to the sacral spinal cord, limiting detrusor overactivity and resulting in clinical alleviation of urine frequency and urgency [ 31 , 32 ]. Electrical stimulation of the pelvic nerve, pudendal nerve sensory fibers, or muscular nerve fibers from lower limbs like the posterior tibial nerve can inhibit spinal micturition centers [ 33 , 34 ].…”

Early Transcutaneous Tibial Nerve Stimulation Acutely Improves Lower Urinary Tract Function in Spinal Cord Injured Rats

“…This possibility is well in line with the current literature in animal research, which shows different outcomes based on a variety of stimulation parameters, including frequency. 36 …”

Prolonged Inhibitory Effects of Repeated Tibial Nerve Stimulation on the Micturition Reflex in Decorticated Rats

“…23 Therefore, the accuracy of most existing studies is limited because of the use of anesthetized animals for micturition reflex evaluation. 17 Although Park et al 13 have reported a poststimulation inhibitory effect of TNS for an average of ten hours in unanesthetized active rats by using an implantable electrical stimulator and a wireless power delivery system, it is difficult to rule out interference from other stimuli in conscious animals, such as body movement, pain, and fear, resulting in significant between-subject discrepancy and inaccurate results. In this context, the decorticated rat model can overcome these limitations.…”

“…Moreover, it is difficult to keep the stimulator still for a long time in an unanesthetized, vigorous animal for outside bladder stimulation and the body movement of experimental animals may affect the results, leading to a significant between-subject discrepancy. In the study by Park et al, 13 the poststimulation inhibitory effect showed a large discrepancy in inhibitory duration for each animal (3-25 hours). Therefore, further studies with a more reliable animal model are needed to determine the prolonged poststimulation inhibitory effect of TNS.…”

“…Notably, a recent study using an implantable electrical stimulator and a wireless power delivery system showed that continuous TNS at 10 Hz for 30 minutes induced a poststimulation inhibitory effect of ten hours in unanesthetized conscious rats. 13 However, conscious animals may be sensitive to other stimuli, such as pain and fear, thus biasing the results. Moreover, it is difficult to keep the stimulator still for a long time in an unanesthetized, vigorous animal for outside bladder stimulation and the body movement of experimental animals may affect the results, leading to a significant between-subject discrepancy.…”