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Opioid analgesics (e.g., fentanyl, morphine, etorphine, buprenorphine, methadone, butorphanol, oxymorphone) have been demonstrated to increase A-a gradient in a variety of species including humans 136,137,138 , goats 139 , rabbits 140 , dogs 141 , impala 142 , and rats 15,94,95