Moderated Poster Session IV: Basic Science & Education

摘要

Background: The role of 5-HT2 and opioid receptors in pudendal inhibitionof bladder activity induced by intravesical infusion of saline or 0.25%acetic acid (AA) was investigated in anesthetized cats using methysergide (a5-HT2 receptor antagonist) and naloxone (an opioid receptor antagonist).Methods: Repeat cystometrograms (CMG’s) were performed in 20 alphachloraloseanesthetized cats by infusing the bladder with saline or 0.25%acetic acid (AA). Pudendal nerve stimulation at multiples of threshold(T) intensity for inducing observable anal twitch was used to suppressAA-induced bladder overactivity. Various doses of methysergide and naloxonewere administered prior to CMG’s.Results: AA irritated the bladder and significantly (p0.0001) reduced bladdercapacity to 27.0±7.4% of saline control capacity. Pudendal nerve stimulation(PNS) at multiples of threshold (T) intensity for inducing anal sphinctertwitching restored bladder capacity to 60.1± 8.0% at 1-2T (p0.0001) and92.2±14.1% at 3-4T (p=0.001) of the saline control capacity. Methysergide(0.03-1 mg/kg, i.v.) suppressed low intensity (1-2T) PNS inhibition but nothigh intensity (3-4T) inhibition, and also significantly (p0.05) increasedcontrol bladder capacity at the dosage of 0.3-1 mg/kg. During saline infusionwithout AA irritation, PNS significantly increased bladder capacity to150.8±9.9% at 1-2T (p0.01) and 180.4±16.6% at 3-4T (p0.01) of thesaline control capacity. Methysergide (0.1-1 mg/kg) significantly (p0.05)increased saline control bladder capacity and suppressed PNS inhibitionat the dosage of 0.03-1 mg/kg. After methysergide treatment (1 mg/kg),naloxone significantly (p0.05) reduced control bladder capacity duringAA infusion but had no effect during saline infusion. Naloxone also hadno influence on PNS inhibition.Conclusions: These results suggest that 5-HT2 receptors play a role in PNSinhibition of reflex bladder activity and interact with opioid receptors inmicturition reflex pathway. Understanding neurotransmitter mechanismsunderlying pudendal neuromodulation is important for the developmentof new treatments for bladder disorders.