(i) additive analgesia in somatic pain assays and supra-additive analgesia in visceral pain paradigms, along with a reduction in adverse side effects such as respiratory depression, and tolerance, dependence and hyperalgesia from chronic MOR agonist treatment was attenuated by pretreatment with a KOR agonist ([14, 15, 17–19, 50, 53, 55–58], see also [67]);. This evidence concerns the gene OPRK1 and respiratory depression.