This lower efficacy may be due to mu opioid receptor (MOR) downregulation in pain pathways, such as dorsal root ganglion (DRG) and spinal cord, after a lesion or disease of the somatosensory nervous system (e.g., an episode of acute herpes zoster, traumatic nerve injury or neuropathy in diabetes) (Zhang et al., 1998; Takasaki et al., 2006; Lee et al., 2011; Mo et al., 2018; Deshpande et al., 2021). This evidence concerns the gene OPRM1 and neuropathy.