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Downregulation of Opioid Receptors after Repeated Opioid Treatment Long-term repeated use of opioids, such as morphine, can lead to analgesic tolerance in patients, which is a major factor that reduces the opioid effect and is also one of the important reasons limiting application in various pain-related diseases [14,42,43,50]

When mitochondrial function is impaired, it can lead to reduced energy availability, oxidative stress, and contributes to a range of metabolic disorders, including insulin resistance and obesity