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.