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However, its prolonged use is associated with a major and challenging side effectmorphine tolerance ( Traditionally, research on the mechanisms of morphine tolerance has primarily focused on neurons, particularly involving -opioid receptor (MOR) desensitization, internalization dysfunction, and compensatory upregulation of intracellular cyclic adenosine monophosphate (cAMP) signaling and other adaptive neuronal changes (Zhang et al., 2023

Because TG2 activity is highly associated with cellular redox status and alterations in the bidirectional flux of cellular thiol modulate TG2 activity, regulation of thiol flux in cells probably affects the TG2-mediated aggregation of the GST tag and its interaction with cellular proteins