Effect Of MrgC RNAi On Morphine-induced Regulation Of CGRP And EAAC1 MRNAs In Dorsal Root Ganglia Of Rats

Mas-related G protein-coupled receptors (Mrg receptor) is uniquely located in the small diameter neurons in dorsal root ganglia (DRG) and trigeminal ganglia (TG), suggesting that these receptors are involved in nociceptive information processing or opioid analgesia. Previous studies in our laboratory have demonstrated that activation of rMrgC modulates the development of morphine tolerance.The present study was designed to investigate the mechanisms of modulation of rMrgC on morphine tolerance. We used techniques of cell culture and RT-PCR to determine the effects of rMrgC SiRNA on morphine-induced increase in CGRP and EAAC1 mRNAs. Six-day treatment with morphine significantly induced an increase in CGRP and EAAC1 mRNAs in cultured DRG explants. However, rMrgC SiRNA application for four days remarkably inhibited these increases. In contrast, control SiRNA did not alter the morphine-induced increase of CGRP and EAAC1 mRNAs.As it has been well cocumented that enhancement of CGRP and EAAC1 at the spinal level plays an important role in the development of morphine tolerance, we conclude that inhibition of rMrgC on the morphine-induced increase of CGRP and suppression of EAAC1 could underly the modulation of rMrgC on morphine tolerance.