Involvement of the 3′ non-coding region of the mu opioid receptor gene in morphine-induced analgesia

The mu opioid receptor (MOR) is known to play an essential role in morphine-induced analgesia. MOR-1 mRNA, the major MOR transcript, possesses a long 3′ untranslated region (3′UTR) in both mouse and human species. The sequence of the MOR-1 3′UTR, especially that of its 3′ end region, is conserved between mice and humans. In the MOR-1 3′UTR, AU-rich elements (AREs) are densely localized at the 3′ end region, suggesting low stability of this mRNA. Numerous putative transcription factor-binding motifs are located in the 3′ non-coding regions of the mouse and human MOR genes. The CXBK mouse strain, known as a MOR-deficient strain, possesses a decreased amount of MOR-1 mRNA containing an abnormally long MOR-1 3′UTR with a long nucleotide insertion. This insert might disrupt the stability of the MOR-1 mRNA or might reduce the transcription of the MOR-1 mRNA by separating the transcription factor-binding motifs in the 3′ non-coding region of the MOR gene, thereby decreasing MOR-1 mRNA expression and attenuating morphine-induced analgesia in CXBK mice. These recent findings suggest that the MOR-1 3′UTR is involved in mRNA expression and in the difference in response to morphine. This possible genetic mechanism may provide a good starting point for designing effective pain treatments with opiates.