Journal article
Metabotropic glutamate receptor 5 (mGluR5) regulates bladder nociception
Molecular pain, Vol.8(1), pp.20-20
03/26/2012
DOI: 10.1186/1744-8069-8-20
PMID: 22449017
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 noninflammatory 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 noninflammatory bladder nociception, and highlight the therapeutic potential for mGluR5 antagonists in the alleviation of bladder pain.
Details
- Title: Subtitle
- Metabotropic glutamate receptor 5 (mGluR5) regulates bladder nociception
- Creators
- Lara W. Crock - Washington University in St. LouisKristina M. Stemler - Washington University in St. LouisDavid G. Song - Saint Louis UniversityPhilip Abbosh - Washington University in St. LouisSherri K. Vogt - Washington University in St. LouisChang-Shen Qiu - Washington University in St. LouisH. Henry Lai - Washington University in St. LouisIndira U. Mysorekar - Washington University in St. LouisRobert W. Gereau - Washington University in St. Louis
- Resource Type
- Journal article
- Publication Details
- Molecular pain, Vol.8(1), pp.20-20
- DOI
- 10.1186/1744-8069-8-20
- PMID
- 22449017
- NLM abbreviation
- Mol Pain
- ISSN
- 1744-8069
- eISSN
- 1744-8069
- Publisher
- Sage
- Number of pages
- 13
- Grant note
- P30NS057105 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) DK089969; T32-A1007172; DK082315; DK082315-02S1; NS48602; DK080643 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Washington University Department of Surgery St Louis Veterans Affairs Medical Center Hope Center for Neurological Disorders Alafi Neuroimaging Laboratory K99DK080643 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) P30 NS057105 / NIH Neuroscience Blueprint Center; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 03/26/2012
- Academic Unit
- Urology
- Record Identifier
- 9985244663802771
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