Metabotropic glutamate receptor 5 (mGluR5) regulates bladder nociception

Lara W. Crock, Kristina M. Stemler, David G. Song, Philip Abbosh, Sherri K. Vogt, Chang Shen Qiu, H. Henry Lai, Indira U. Mysorekar, Robert W. Gereau IV

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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.

Original languageEnglish
Article number20
JournalMolecular Pain
Volume8
DOIs
StatePublished - Mar 26 2012

Keywords

  • Bladder
  • Metabotropic glutamate receptor
  • Nociception
  • Urinary tract infection
  • Visceromotor response

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