Contribution of opioid and metabotropic glutamate receptor mechanisms to inhibition of bladder overactivity by tibial nerve stimulation

Am J Physiol Regul Integr Comp Physiol. 2013 Jul 15;305(2):R126-33. doi: 10.1152/ajpregu.00572.2012. Epub 2013 Apr 10.

Abstract

The contribution of metabotropic glutamate receptors (mGluR) and opioid receptors to inhibition of bladder overactivity by tibial nerve stimulation (TNS) was investigated in cats under α-chloralose anesthesia using LY341495 (a group II mGluR antagonist) and naloxone (an opioid receptor antagonist). Slow infusion cystometry was used to measure the volume threshold (i.e., bladder capacity) for inducing a large bladder contraction. After measuring the bladder capacity during saline infusion, 0.25% acetic acid (AA) was infused to irritate the bladder, activate the nociceptive C-fiber bladder afferents, and induce bladder overactivity. AA significantly (P < 0.0001) reduced bladder capacity to 26.6 ± 4.7% of saline control capacity. TNS (5 Hz, 0.2 ms) at 2 and 4 times the threshold (T) intensity for inducing an observable toe movement significantly increased bladder capacity to 62.2 ± 8.3% at 2T (P < 0.01) and 80.8 ± 9.2% at 4T (P = 0.0001) of saline control capacity. LY341495 (0.1-5 mg/kg iv) did not change bladder overactivity, but completely suppressed the inhibition induced by TNS at a low stimulus intensity (2T) and partially suppressed the inhibition at high intensity (4T). Following administration of LY341495, naloxone (0.01 mg/kg iv) completely eliminated the high-intensity TNS-induced inhibition. However, without LY341495 treatment a 10 times higher dose (0.1 mg/kg) of naloxone was required to completely block TNS inhibition. These results indicate that interactions between group II mGluR and opioid receptor mechanisms contribute to TNS inhibition of AA-induced bladder overactivity. Understanding neurotransmitter mechanisms underlying TNS inhibition of bladder overactivity is important for the development of new treatments for bladder disorders.

Keywords: bladder; cat; neuromodulation; neurotransmitter.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acids / pharmacology
  • Animals
  • Cats
  • Electric Stimulation Therapy / methods
  • Excitatory Amino Acid Antagonists / pharmacology
  • Female
  • Male
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Receptors, Metabotropic Glutamate / metabolism*
  • Receptors, Opioid / metabolism*
  • Tibial Nerve / physiology*
  • Urinary Bladder / drug effects
  • Urinary Bladder / metabolism*
  • Urinary Bladder, Overactive / metabolism*
  • Urinary Bladder, Overactive / physiopathology
  • Urinary Bladder, Overactive / therapy
  • Xanthenes / pharmacology

Substances

  • Amino Acids
  • Excitatory Amino Acid Antagonists
  • LY 341495
  • Narcotic Antagonists
  • Receptors, Metabotropic Glutamate
  • Receptors, Opioid
  • Xanthenes
  • Naloxone