PURPOSE: To determine the role of opioid and metabotropic glutamate 5 receptors (mGluR5) in pudendal inhibition of bladder overactivity.
MATERIALS AND METHODS: Cystometrograms (CMGs) were performed in 11 cats underα-chloralose anesthesia by slowly infusing the bladder with saline or 0.25% acetic acid (AA). Pudendal nerve stimulation at intensities of multiple times the threshold (T) to induce observable anal twitching was applied during CMGs to inhibit the bladder overactivity induced by AA irritation. Naloxone (0.1, 0.3, and 1 mg/kg, i.v.) was administered to block opioid receptors followed by MTEP (3 and 10 mg/kg, i.v.) administration to block mGluR5 receptors. After each dose of drug, pudendal inhibition of bladder overactivity was examined during CMGs.
RESULTS: AA irritated the bladder, induced bladder overactivity, and significantly (P< 0.0001) reduced bladder capacity to 23.6±2.7%% of saline control capacity. Pudendal nerve stimulation at 1-1.5T and 4T suppressed bladder overactivity and significantly increased the capacity to 57.5±8.1% (P=0.0005) and 106±15% (P=0.0002), respectively, of the saline control capacity. Naloxone had no effect on pudendal inhibition, but MTEP eliminated the inhibition induced by low intensity stimulation and significantly (P< 0.05) reduced the inhibition induced by high intensity stimulation. Neither naloxone or MTEP altered baseline bladder overactivity.
CONCLUSION: Opioid receptors are not involved in pudendal inhibition of bladder overactivity, but mGluR5 receptors are partially involved. Understanding neurotransmitter mechanisms could improve the efficacy of neuromodulation therapy for overactive bladder (OAB) treatment, and identify molecular targets for development of new drugs for treating OAB.
Written by:
Mally AD, Matsuta Y, Zhang F, Shen B, Wang J, Roppolo JR, de Groat WC, Tai C. Are you the author?
Department of Urology, University of Pittsburgh, Pittsburgh, PA.
Reference: J Urol. 2012 Sep 25. pii: S0022-5347(12)04990-7.
doi: 10.1016/j.juro.2012.09.095
PubMed Abstract
PMID: 23022006
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