“…The recent identification and characterization of several opioid receptor isoforms generated through alternative splicing of opioid receptor-encoding genes, particularly the m-opioid receptor-encoding OPRM1, has led to a more conclusive explanation for the discrepancies observed in opioid pharmacology, as structural differences between isoforms result in unique agonist selectivity, constitutive activity, agonistmediated signaling, and internalization. Furthermore, these isoforms, in conjunction with several SNPs, are understood to have important physiological signifigance in opioid sensitivity and addiction (Lotsch and Geisslinger, 2005;Kreek and LaForge, 2007;Klein et al, 2009), as some polymorphisms in the MOR-1K (Shabalina et al, 2009;Diatchenko et al, 2011) and MOR-1X (Pang et al, 2012) variants have been found to alter opioid drug response, while others have not (Smith et al, 2005;Mayer and Hollt, 2006). Therefore, opioid receptor isoforms must be regarded as separate receptor subtypes that collectively contribute to the overall cellular and physiological effects of opioids and differential expression of these isoforms will alter opioid pharmacology accordingly.…”