Role of μ, Κ, and δ opioid receptors in tibial inhibition of bladder overactivity in cats

Abstract

In a-chloralose anesthetized cats, we examined the role of opioid receptor (OR) subtypes (μ, Κ, and δ) in tibial nerve stimulation (TNS)-induced inhibition of bladder overactivity elicited by intravesical infusion of 0.25% acetic acid (AA). The sensitivity of TNS inhibition to cumulative i.v. doses of selective OR antagonists (cyprodime for μ, nor-binaltorphimine for Κ, or naltrindole for δ ORs) was tested. 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 pretreated cats, but it reversed the nor-binaltorphimine-induced increase in bladder capacity and eliminated the TNS inhibition remaining in naltrindole pretreated cats. These results indicate a major role of m and k ORs in TNS inhibition, whereas d ORs play a minor role. Meanwhile, Κ and d ORs also have an excitatory role in irritation-induced bladder overactivity.