The Epigenetic Regulation of the Opioid System: New Individualized Prompt Prevention and Treatment Strategies

Abstract

The most well-known physiological effect associated with opiod system is their efficacy in pain reduction or analgesia, although their effect on a variety of other physiological and physiophological functions has become apparent in recent years. This review is an attempt to clarify in more detail the epigenetic regulation of opioid system to understand with more precision their transcriptional and posttranscriptional regulation in multiple pyisiological and pharmacological contexts. The opioid receptors show an epigenetic regulation and opioid peptide precursors by methylation, chromatin remodeling and microRNA. Although the opioid receptor promoters have similarity between them, they use different epigenetic regulation forms and they exhibit different pattern of expression during the cell differentiation. DNA methylation is also confirmed in opioid peptide precursors, being important for gene expression and tissue specificity. Understanding the epigenetic basis of those physiological and physiopathological procesess is essential for the development of individualized prompt prevention and treatment strategies.

A new mechanistic approach for the treatment of chronic neuropathic pain with nitrous oxide integrated from a systems biology narrative review

“…For example, when S-adenosylmethionine is downregulated, the downstream transcriptional effect is to increase production of δ- and κ-opioid ligands (principally met-enkephalin) at the expense of µ-receptor peptides (β-endorphin) and nociceptin. 92 A reduction in DNA methylation may also increase the expression of DOR and μ-opioid receptors (MOR), but does not affect κ opioid receptor expression, which is regulated by histone acetylation. 93 …”

The Role of Epigenetics and Contributing Impact of Stress, Multigenerational, and Developmental Factors in Opiate Addiction

“…Endorphins, enkephalins, dynorphins, and endomorphins are endogenous opioid peptides that originate from their precursors, pro-opiomelanocortin, proenkephalin, and prodynorphin, to induce activity via opioid receptors. Previous studies have shown that opioid receptor alleles have characteristics that make them more susceptible to epigenetic regulation, e.g., genes that are rich in CpG islands: regions that contain cytosine-guanine dinucleotides where cytosine is susceptible to methylation [6]. This enables modification of promoter regions as well as chromatin remodeling that modulates expression [6].…”

“…Previous studies have shown that opioid receptor alleles have characteristics that make them more susceptible to epigenetic regulation, e.g., genes that are rich in CpG islands: regions that contain cytosine-guanine dinucleotides where cytosine is susceptible to methylation [6]. This enables modification of promoter regions as well as chromatin remodeling that modulates expression [6]. Continuing this line of study, it may be possible to determine how environmental, developmental, stressor, or transgenerational factors explain today's "risk factors" and even preventive or clinical intervention for opiate addiction.…”

Epigenetic Modulation of Opioid Receptors by Drugs of Abuse

“…Changes in the expression of opioid receptors have been associated with increased vulnerability to drug-seeking and taking behavior in both human and animal models of SUD [ 3 , 4 ]. Early studies in cultured cells demonstrated that opioid receptors are subject to epigenetic regulations [ 5 ]. Since it has become increasingly appreciated that drugs of abuse modify epigenetic regulation in the brain [ 6 , 7 ], this review summarizes the mechanisms underlying epigenetic modulations of opioid receptor subtypes in the context of SUD, which has not been reviewed previously.…”