Limits...
Metabotropic glutamate receptor 5 (mGluR5) regulates bladder nociception.

Crock LW, Stemler KM, Song DG, Abbosh P, Vogt SK, Qiu CS, Lai HH, Mysorekar IU, Gereau RW - Mol Pain (2012)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Neuroscience Program, Washington University School of Medicine, St, Louis, MO 63110, USA.

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.

Show MeSH

Related in: MedlinePlus

mGluR5 KO mice have an increased intermicturition interval. A. Representative urodynamic profile of a WT mouse. B. Representative urodynamic profile of a mGluR5 KO mouse. A-C. The IMI in WT mice was significantly smaller when compared to mGluR5 KO mice (WT baseline IMI 212.3 ± 12.94 N = 3, mGluR5 KO IMI baseline 471.5 ± 29.14 N = 5). D. However, there was no difference in the bladder contraction amplitude. ***P < 0.001 unpaired Student's t-test compared to WT IMI.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3369204&req=5

Figure 3: mGluR5 KO mice have an increased intermicturition interval. A. Representative urodynamic profile of a WT mouse. B. Representative urodynamic profile of a mGluR5 KO mouse. A-C. The IMI in WT mice was significantly smaller when compared to mGluR5 KO mice (WT baseline IMI 212.3 ± 12.94 N = 3, mGluR5 KO IMI baseline 471.5 ± 29.14 N = 5). D. However, there was no difference in the bladder contraction amplitude. ***P < 0.001 unpaired Student's t-test compared to WT IMI.

Mentions: To test the role of mGluR5 in urodynamics, we compared the cystometry profile of mGluR5 KO mice and their WT littermates. mGluR5 KO mice had a significantly increased IMI (212.3 seconds versus 471.5 seconds, for WT and KO, respectively, p = 0.0006) (Figure 3A-C). Despite the difference in IMI, the average amplitude of bladder contractions was not significantly different in mGluR5 KO mice relative to their WT littermates (Figure 3D, p = 0.9215).


Metabotropic glutamate receptor 5 (mGluR5) regulates bladder nociception.

Crock LW, Stemler KM, Song DG, Abbosh P, Vogt SK, Qiu CS, Lai HH, Mysorekar IU, Gereau RW - Mol Pain (2012)

mGluR5 KO mice have an increased intermicturition interval. A. Representative urodynamic profile of a WT mouse. B. Representative urodynamic profile of a mGluR5 KO mouse. A-C. The IMI in WT mice was significantly smaller when compared to mGluR5 KO mice (WT baseline IMI 212.3 ± 12.94 N = 3, mGluR5 KO IMI baseline 471.5 ± 29.14 N = 5). D. However, there was no difference in the bladder contraction amplitude. ***P < 0.001 unpaired Student's t-test compared to WT IMI.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3369204&req=5

Figure 3: mGluR5 KO mice have an increased intermicturition interval. A. Representative urodynamic profile of a WT mouse. B. Representative urodynamic profile of a mGluR5 KO mouse. A-C. The IMI in WT mice was significantly smaller when compared to mGluR5 KO mice (WT baseline IMI 212.3 ± 12.94 N = 3, mGluR5 KO IMI baseline 471.5 ± 29.14 N = 5). D. However, there was no difference in the bladder contraction amplitude. ***P < 0.001 unpaired Student's t-test compared to WT IMI.
Mentions: To test the role of mGluR5 in urodynamics, we compared the cystometry profile of mGluR5 KO mice and their WT littermates. mGluR5 KO mice had a significantly increased IMI (212.3 seconds versus 471.5 seconds, for WT and KO, respectively, p = 0.0006) (Figure 3A-C). Despite the difference in IMI, the average amplitude of bladder contractions was not significantly different in mGluR5 KO mice relative to their WT littermates (Figure 3D, p = 0.9215).

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Neuroscience Program, Washington University School of Medicine, St, Louis, MO 63110, USA.

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.

Show MeSH
Related in: MedlinePlus