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Effect of Mas-related gene (Mrg) receptors on hyperalgesia in rats with CFA-induced inflammation via direct and indirect mechanisms.

Authors: Jiang, J  Wang, D  Zhou, X  Huo, Y  Chen, T  Hu, F  Quirion, R  Hong, Y 
Citation: Jiang J, etal., Br J Pharmacol. 2013 Aug 2. doi: 10.1111/bph.12326.
Pubmed: (View Article at PubMed) PMID:23909597
DOI: Full-text: DOI:10.1111/bph.12326

BACKGROUND AND PURPOSE: Mrg receptors are exclusively distributed in small-sized neurons in trigeminal and dorsal root ganglia (DRG). We investigated the effects of MrgC receptor activation on inflammatory hyperalgesia and its mechanisms. EXPERIMENTAL APPROACH: Selective MrgC receptor agonist BAM8-22 or MSH or mu-opioid receptor antagonist CTAP was administered intrathecally (i.t.) in rats treated with injection of CFA in hindpaw. Thermal and mechanical nociceptive behaviours were assessed. Expressions of neurochemicals were measured by immunocytochemistry, Western blot, ELISA and RT-PCR. KEY RESULTS: CFA injection induced an increase in MrgC receptor mRNA in lumbar DRG. I.t. administration of BAM8-22 or MSH generated instant short and delayed long-lasting attenuations of CFA-induced thermal hyperalgesia, but not mechanical allodynia. These effects were associated with the inhibition of upregulation of nNOS and CGRP as well as c-Fos expression in the spinal dorsal horn and/or DRG. However, i.t. administration of BAM8-22 failed to induce the delayed anti-hyperalgesia and inhibition of nNOS and CGRP expressions in DRG in the presence of CTAP. The i.t. BAM8-22 also induced an increase in mRNAs coding for mu-opioid receptors and proopiomelanocortin as well as beta-endorphin content in the lumbar spinal cord and/or DRG. The co-localization of MrgC receptors and nNOS was seen in DRG neurons. CONCLUSIONS AND IMPLICATIONS: Activation of MrgC receptors can suppress upregulation of pronociceptive mediators leading to the inhibition of inflammatory pain which are attributed to the activation of upregulated MrgC receptors and subsequent recruitment of endogenous mu-opioidergic activity. The uniquely distributed MrgC receptors could be a novel target for relieving inflammatory pain.

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RGD Object Information
RGD ID: 7257597
Created: 2013-08-27
Species: All species
Last Modified: 2013-08-27
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.