Metabotropic glutamate receptor 5 (mGluR5) regulates bladder nociception

Mol Pain. 2012 Mar 26;8:20. doi: 10.1186/1744-8069-8-20.

Abstract

Background: Interstitial cystitis/painful bladder syndrome (IC/PBS), is a severely debilitating chronic condition that is frequently unresponsive to conventional pain medications. The etiology is unknown, however evidence suggests that nervous system sensitization contributes to enhanced pain in IC/PBS. In particular, central nervous system plasticity of glutamatergic signaling involving NMDA and metabotropic glutamate receptors (mGluRs) has been implicated in a variety of chronic pain conditions. Here, we test the hypothesis that mGluR5 mediates both non-inflammatory and inflammatory bladder pain or nociception in a mouse model by monitoring the visceromotor response (VMR) during graded bladder distention.

Results: Using a combination of genetic and pharmacologic approaches, we provide evidence indicating that mGluR5 is necessary for the full expression of VMR in response to bladder distention in the absence of inflammation. Furthermore, we observed that mice infected with a uropathogenic strain of Escherichia coli (UPEC) develop inflammatory hyperalgesia to bladder distention, and that the selective mGluR5 antagonist fenobam [N-(3-chlorophenyl)-N'-(4,5-dihydro-1-methyl-4-oxo-1H-imidazole-2-yl) urea], reduces the VMR to bladder distention in UPEC-infected mice.

Conclusions: Taken together, these data suggest that mGluR5 modulates both inflammatory and non-inflammatory bladder nociception, and highlight the therapeutic potential for mGluR5 antagonists in the alleviation of bladder pain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Central Nervous System / drug effects
  • Central Nervous System / metabolism
  • Escherichia coli / pathogenicity
  • Female
  • Imidazoles / pharmacology
  • Imidazoles / therapeutic use
  • Mice
  • Mice, Inbred C57BL
  • Nociception / drug effects*
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / metabolism*
  • Urinary Bladder / drug effects
  • Urinary Bladder / microbiology
  • Urinary Tract Infections / metabolism
  • Urodynamics

Substances

  • Grm5 protein, mouse
  • Imidazoles
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • fenobam