AB260. Role of µ, κ, and δ opioid receptors in tibial inhibition of bladder overactivity in cats

BACKGROUND: To study the impact of µ, κ, and δ opioid receptors on tibial inhibition of bladder overactivity in cats METHODS: In α-chloralose anesthetized cats we examined the role of opioid receptor (OR) subtypes (µ, κ, and δ) intibialnerve stimulation (TNS) induced inhibition of bladder overactivity elicited by intravesical infusion of 0.25% acetic acid (AA). The sensitivity of TNS inhibition to cumulative intravenous doses of selective OR antagonists (cyprodime for µ, nor-binaltorphimine for κ, or naltrindole for δ ORs) was tested. RESULTS: Naloxone (1 mg/kg, i.v., an antagonist for µ, κ, and δ ORs) was administered at the end of each experiment. AA caused bladder overactivity and significantly (P<0.01) reduced bladder capacity to 21.1±2.6% of the saline control. TNS at 2 or 4 times threshold (T) intensity for inducing toe movement significantly (P<0.01) restored bladder capacity to 52.9±3.6% or 57.4±4.6% of control, respectively. Cyprodime (0.3–1.0 mg/kg) completely removed TNS inhibition without changing AA control capacity. Nor-binaltorphimine (3–10 mg/kg) also completely reversed TNS inhibition and significantly (P<0.05) increased AA control capacity. Naltrindole(1–10 mg/kg) reduced (P<0.05) TNS inhibition but significantly (P<0.05) increased AA control capacity. Naloxone (1 mg/kg) had no effect in cyprodime pre-treated cats, but reversed the nor-binaltorphimine induced increase in bladder capacity and eliminated the TNS inhibition remaining in naltrindole pre-treated cats. CONCLUSIONS: These results indicate a major role of µ and κ ORs in TNS inhibition while δORs play a minor role. Meanwhile, κ and δORs also have an excitatory role in irritation-induced bladder overactivity.