For example, the 7TM variants are essential for morphine analgesia whereas the 6TM variants are not [77] although 6TM variants are important for analgesic effects of other MOR agonists [78] in models of thermal, neuropathic, and inflammatory pain without producing respiratory depression, physical dependence, or reward [79]. This evidence concerns the gene OPRM1 and Respiratory insufficiency due to muscle weakness.