Role of Micro-RNA for Pain After Surgery: Narrative Review of Animal and Human Studies

Abstract

One of the most prevalent symptoms after major surgery is pain. When postoperative pain treatment is unsatisfactory, it can lead to poor surgical recovery, decreased quality of life, and increased health care costs. Current analgesics, single or in combination, have limited efficacy due to low potency, limited duration of action, toxicities, and risk of addiction. The lack of nonaddictive strong analgesics along with the over prescription of opioids has led to an opioid epidemic in the United States. Therefore, there is an urgent need for the development of newer analgesics. Microribonucleic acids (miRNAs) are small noncoding RNA molecules that modulate protein synthesis in neurons and supporting cells (glia, leukocytes, and Schwann cells). The literature indicates that miRNA regulation is important in nociception. Here, we summarize the current evidence on the role of miRNAs on mechanisms involved in incisional, inflammatory, neuropathic, and cancer pain. We also discuss the role of modulating miRNA functions as potential therapeutic targets for analgesic use and opioid tolerance. Finally, we propose how the

Schwann cell-derived extracellular vesicles promote memory impairment associated with chronic neuropathic pain

“…As a double-edged sword, SCs, critical peripheral nervous system components, are continually exposed to physiological and mechanical stressors during movement due to dynamic stretching and compression pressures [ 10 , 11 ]. SC-EVs transmit cargo to promote peripheral nerve regeneration in vitro [ 11 ], but they also play a role in nociceptive hypersensitivity [ 39 ]. Here, we discovered for the first time that, compared to those in sham rats, SC-EVs in the hippocampus were significantly enriched in CNP rats by generating three classic models of CNP, namely CCI, SNI, and SNI (14 days after modeling), overexpressing specific SC promoters using AAVs containing CD63-GFP.…”

Cell-free therapy based on extracellular vesicles: a promising therapeutic strategy for peripheral nerve injury

“…Clinical studies have suggested that EXOs can modulate immune responses and promote the healing process, thereby potentially alleviating inflammation and pain [ 125 ]. Indeed, EXOs can suppress the production of proinflammatory cytokines such as TNF-α,IL-1β, and PGE2 in tissue-injured areas and also stimulate the release of IL-10, leading to antinociceptive effects [ 126 ]. Exosomal miRNAs like miR-181c-5p, miR-216a-5p, and miR-126-3p have also been demonstrated to ameliorate neuropathic pain in sciatic nerve compression in in vivo studies [ 123 , 127 ].…”

Epigenetic Alterations in Prescription Opioid Misuse: New Strategies for Precision Pain Management

“…It is also important to report the role that micro-RNAs (miRNAs) might play in opioid response and pain. In fact, it has been observed that commonly used analgesics altered their expression [63]. One example is miR-339-3p, the expression of which was consistently increased by both morphine and fentanyl.…”

“…Then, it was demonstrated that miR-339-3p destabilizes MOR mRNA and thus inhibits the MOR protein biosynthesis [25]. In nociception, the altered expression of many miRNAs was described in the context of surgical pain models, and some of them were related to morphine tolerance [63]. Chronic morphine treatment was observed to increase BDNF transcription and translation.…”