Neuromodulation versus neurotoxin for the treatment of refractory detrusor overactivity: for neuromodulation

Nakib, Nissrine; Siegel, Steven

doi:10.1038/ncpuro1033

Cited by 10 publications

(14 citation statements)

References 8 publications

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“…This will be directly evaluated in future experiments by testing TNS during voiding CMGs. The selective action of TNS on bladder capacity in anesthetized cats is similar to the clinical observations in OAB patients that different types of neuromodulation improve urine storage without reducing voiding efficiency (3,11,16,30). This selectivity suggests that neuromodulation targets the afferent limb of the micturition reflex or the supraspinal switching mechanism in the PAG-PMC circuitry but does not alter the efferent (motor) limb of the circuit.…”

Section: Discussionsupporting

confidence: 73%

Role of the brain stem in tibial inhibition of the micturition reflex in cats

Ferroni

Slater

Shen

et al. 2015

American Journal of Physiology-Renal Physiology

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This study examined the role of the brain stem in inhibition of bladder reflexes induced by tibial nerve stimulation (TNS) in ␣-chloralose-anesthetized decerebrate cats. Repeated cystometrograms (CMGs) were performed by infusing saline or 0.25% acetic acid (AA) to elicit normal or overactive bladder reflexes, respectively. TNS (5 or 30 Hz) at three times the threshold (3T) intensity for inducing toe movement was applied for 30 min between CMGs to induce post-TNS inhibition or applied during the CMGs to induce acute TNS inhibition. Inhibition was evident as an increase in bladder capacity without a change in amplitude of bladder contractions. TNS applied for 30 min between saline CMGs elicited prolonged (Ͼ2 h) poststimulation inhibition that significantly (P Ͻ 0.05) increased bladder capacity to 30 -60% above control; however, TNS did not produce this effect during AA irritation. TNS applied during CMGs at 5 Hz but not 30 Hz significantly (P Ͻ 0.01) increased bladder capacity to 127.3 Ϯ 6.1% of saline control or 187.6 Ϯ 5.0% of AA control. During AA irritation, naloxone (an opioid receptor antagonist) administered intravenously (1 mg/kg) or directly to the surface of the rostral brain stem (300 -900 g) eliminated acute TNS inhibition and significantly (P Ͻ 0.05) reduced bladder capacity to 62.8 Ϯ 22.6% (intravenously) or 47.6 Ϯ 25.5% (brain stem application). Results of this and previous studies indicate 1) forebrain circuitry rostral to the pons is not essential for TNS inhibition; and 2) opioid receptors in the brain stem have a critical role in TNS inhibition of overactive bladder reflexes but are not involved in inhibition of normal bladder reflexes. neuromodulation; brain stem; opioid; tibial; cat TIBIAL NEUROMODULATION, a Food and Drug Administration (FDA)-approved therapy for overactive bladder (OAB) symptoms, including urgency, frequency, and incontinence (7,19,20,29), is often used to treat patients whose symptoms are not completely controlled by drugs or who have unacceptable drug side effects (1,2,8,18). However, the mechanisms underlying tibial neuromodulation therapy are uncertain. Understanding the site of action and neurotransmitters involved in the inhibition of bladder reflexes by tibial nerve stimulation (TNS) is important for developing new OAB treatments by combining drug therapies with tibial neuromodulation to achieve a higher efficacy with fewer side effects (14,33).Previous studies in cats have demonstrated the inhibitory effect of TNS on bladder reflexes elicited during non-nociceptive saline distention as well as nociceptive acetic acid (AA) irritation (23,27). The failure of TNS to inhibit reflex bladder contractions during AA irritation in animals with acute spinal cord transection at the T9/T10 level (32) indicates that supraspinal neural circuits are necessary for TNS inhibition. However, it is unknown whether these supraspinal circuits are located in the forebrain or in the brain stem.A major clinical benefit of TNS is the long-lasting poststimulation inhibitory effect, which allows...

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Section: Discussionsupporting

confidence: 73%

Role of the brain stem in tibial inhibition of the micturition reflex in cats

Ferroni

Slater

Shen

et al. 2015

American Journal of Physiology-Renal Physiology

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“…3) translate to humans, then the clinical dosage of tramadol necessary for treating OAB could be significantly reduced when combined with tibial neuromodulation, thereby significantly reducing or eliminating the adverse effects of tramadol. The proposed combined new treatment strategy also provides significant advantages over sacral or tibial neuromodulation alone because sacral neuromodulation, which has a high efficacy in OAB treatment, is invasive, requiring surgery to implant the stimulator and electrode (13,35). Tibial neuromodulation is minimally invasive, only requiring insertion of a needle electrode at the ankle to stimulate the tibial nerve, but its efficacy is lower than sacral neuromodulation (10,19).…”

Section: Discussionmentioning

confidence: 99%

“…Currently, antimuscarinic drugs are the primary pharmacological treatment for OAB; however, these agents elicit significant adverse effects and, in turn, a high patient dropout rate (1,9). Sacral neuromodulation is an alternative treatment option for OAB refractory to pharmacotherapy, but it requires surgery (13,35). Tibial nerve stimulation (TNS) is also useful in treating OAB and is minimally invasive, but its efficacy is relatively low (10,19).…”

mentioning

confidence: 99%

Inhibition of bladder overactivity by a combination of tibial neuromodulation and tramadol treatment in cats

Zhang

Mally

Ogagan

et al. 2012

American Journal of Physiology-Renal Physiology

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Our recent study in cats revealed that inhibition of bladder overactivity by tibial nerve stimulation (TNS) depends on the activation of opioid receptors. TNS is a minimally invasive treatment for overactive bladder (OAB), but its efficacy is low. Tramadol (an opioid receptor agonist) is effective in treating OAB but elicits significant adverse effects. This study was to determine if a low dose of tramadol (expected to produce fewer adverse effects) can enhance the TNS inhibition of bladder overactivity. Bladder overactivity was induced in α-chloralose-anesthetized cats by an intravesical infusion of 0.25% acetic acid (AA) during repeated cystometrograms (CMGs). TNS (5 Hz) at two to four times the threshold intensity for inducing toe movement was applied during CMGs before and after tramadol (0.3–7 mg/kg iv) to examine the interaction between the two treatments. AA irritation significantly reduced bladder capacity to 24.8 ± 3.3% of the capacity measured during saline infusion. TNS alone reversibly inhibited bladder overactivity and significantly increased bladder capacity to 50–60% of the saline control capacity. Tramadol administered alone in low doses (0.3–1 mg/kg) did not significantly change bladder capacity, whereas larger doses (3–7 mg/kg) increased bladder capacity (50–60%). TNS in combination with tramadol (3–7 mg/kg) completely reversed the effect of AA. Tramadol also unmasked a prolonged (>2 h) TNS inhibition of bladder overactivity that persisted after termination of the stimulation. The results suggest a novel treatment strategy for OAB by combining tibial neuromodulation with a low dose of tramadol, which is minimally invasive with a potentially high efficacy and fewer adverse effects.

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“…1 It is known that electrical stimulation of somatic afferent pathways in the pudendal nerve, 2-5 posterior tibial nerve, 6,7 or sacral spinal roots 8,9 can inhibit bladder activity in both humans and animals, and is clinically effective in treating overactive bladder symptoms. However, sacral and pudendal neuromodulation is invasive and requires surgery to implant an electrical stimulator and an electrode (InterStim®, Medtronic Inc., Minneapolis, MN, USA).…”

Section: Introductionmentioning

confidence: 99%

“…However, sacral and pudendal neuromodulation is invasive and requires surgery to implant an electrical stimulator and an electrode (InterStim®, Medtronic Inc., Minneapolis, MN, USA). 2,3,8,9 On the other hand percutaneous tibial nerve neuromodulation is minimally invasive only requiring the insertion of a needle electrode at the ankle to target the tibial nerve, but it requires frequent clinical visits. Following the initial treatment of 30 minute tibial nerve stimulation once per week for 12 weeks, a maintenance treatment of once every 2-3 weeks is usually required.…”

Section: Introductionmentioning

confidence: 99%

Post-Stimulation Inhibitory Effect on Reflex Bladder Activity Induced by Activation of Somatic Afferent Nerves in the Foot

et al. 2012

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Purpose To determine if transcutaneous electrical stimulation of somatic afferent nerves in the foot of cats can induce a post-stimulation increase in bladder capacity. Materials and Methods In α-chloralose anesthetized cats (N=12) electrical stimulation (5 Hz) was applied to the skin of the hind foot for two periods of 30 minutes via dual pad electrodes attached on the plantar and dorsal surfaces (combination 1-2) or at two sites on the plantar surface (combination 1-3). The post-stimulation effect was examined by performing repeated CMGs following 30 minute stimulation. In the control group (N=12) the isovolumetric contractions were allowed to continue during each 30 minute period without stimulation. Results Stimulation inhibited isovolumetric rhythmic bladder contractions. The bladder capacity was not increased after the first 30 minute foot stimulation via electrode combination 1-2, but was significantly increased 47.5±2.9% after the second 30 minute stimulation via electrode combination 1-3. After inducing the post-stimulation effect, the foot stimulation applied during CMGs via electrode combinations 1-2 or 1-3 elicited a further increase in bladder capacity (23.26±17.64% and 20.07±18.59% respectively). Conclusions This study shows that the transcutaneous plantar electrical stimulation of somatic afferent nerves in the foot can induce a post-stimulation increase in bladder capacity, suggesting that an intermittent stimulation pattern rather than a continuous stimulation might be effective in clinical applications to treat overactive bladder symptoms.

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Neuromodulation versus neurotoxin for the treatment of refractory detrusor overactivity: for neuromodulation

Cited by 10 publications

References 8 publications

Role of the brain stem in tibial inhibition of the micturition reflex in cats

Role of the brain stem in tibial inhibition of the micturition reflex in cats

Inhibition of bladder overactivity by a combination of tibial neuromodulation and tramadol treatment in cats

Post-Stimulation Inhibitory Effect on Reflex Bladder Activity Induced by Activation of Somatic Afferent Nerves in the Foot

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