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

Zhang F, Mally AD, Ogagan PD, Shen B, Wang J, Roppolo JR, de Groat WC, Tai C. Inhibition of bladder overactivity by a combination of tibial neuromodulation and tramadol treatment in cats. Am J Physiol Renal Physiol 302: F1576-F1582, 2012. First published April 11, 2012; doi: 10.1152/ajprenal.00107.2012.-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 alpha-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 (0.3-7 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.