Abstract
Emerging evidence demonstrates functional contributions of microRNAs (miRNAs) to μ-opioid receptor (MOR) signaling, but the information so far has been mostly limited to their intracellular regulatory mechanisms. The present study aimed to investigate changes in plasma miRNA profiles elicited by opioid treatment in blood samples collected from clinical studies. Healthy male subjects were orally administered with hydromorphone or oxycodone and blood samples were collected at a specified time after the drug treatment. A total of 179 plasma miRNAs were measured using multiplex qRT-PCR. Nine and seventeen miRNAs were commonly upregulated (let-7a-5p, miR-423-3p, miR-199a-3p, miR-146a-5p, miR-23b-3p, miR-24-3p, miR-221-3p, miR-223-3p, and miR-146b-5p) and downregulated (miR-144-3p, miR-215, miR-363-3p, etc.), respectively, following opioid treatment. The MOR signaling-associated miRNAs, namely let-7 family miRNAs (i.e., let-7d-5p, let-7f-5p, let-7c, let-7e-5p), miR-103a-3p, miR-339-3p, miR-146a-5p, miR-23b-3p, miR-23a-3p, and miR-181a-5p, were differentially expressed following drug treatment. These differentially expressed miRNAs are circulating biomarker candidates that can be used to evaluate MOR stimulation and serve as novel clinical diagnostic tools for improving clinical outcomes.
Highlights
Opioids are the most widely used analgesics for the treatment of pain and related disorders
Four distinct opioid receptors have been reported, namely, μ, κ and δ receptors and opioid receptor-like-1 receptor, all of which are classified as G-protein coupled proteins [1]. μ-opioid receptor (MOR) is primarily responsible for opioid analgesia and is encoded by the OPRM1 gene, which can produce various alternatively spliced variants in humans [2]
Opioids are generally effective analgesics for chronic pain, individual variability exists among patients in terms of efficacy and side effects, thereby increasing the demand for personalized medication strategies to maximize patient benefit and cost-effectiveness [3]
Summary
Opioids are the most widely used analgesics for the treatment of pain and related disorders. Opioids have been increasingly used for pain management; their widespread use has been accompanied by increased drug abuse, overdose, and even death [3]. Opioids are generally effective analgesics for chronic pain, individual variability exists among patients in terms of efficacy and side effects, thereby increasing the demand for personalized medication strategies to maximize patient benefit and cost-effectiveness [3]. Imaging technology represents one of the most promising tools that can be applied to investigate the functional dynamics in the central nervous system (CNS) in response to opioid treatment in males [4,5] and is expected to be useful for analgesic drug development. Measurable biomarkers using accessible biological specimens, such as blood, are desired for practical medical use
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