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This results in elevated ROS, increased apoptosis, and impaired autophagy

Surgery involving partial or complete removal of any part of the gastrointestinal tract, including some bariatric surgery procedures, will reduce food-bound B12 absorption and lower serum B12 concentrations

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The multiple cell-death mechanisms activated by ROS generated by exposure to silver have garnered attention of several researchers (28, 29, 32, 34)

Based on this, some mechanistic explanations have been proposed for the loss of strong opioid effectiveness in NP conditions, including the release of dynorphin [67], the downregulation of MOR in the spinal cord [76,77] and dorsal root ganglion (DRG) [78,79], the increase in the serotonin level [80], increased methylation of the MOR gene promoter in DRG and/or the stimulation of glutamate receptor [81], the decrease in morphine concentration in the brain [86], etc