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In the 1970s, sickle cell pain was treated with trial and error approach by increasing or decreasing the dose of an opioid or switching from one analgesic to another. This approach was controversial with criticism and doubt about its usefulness. Since then, advances in determining the structure of opioid receptors and the role of the CYP450 enzymes in metabolizing opioids revealed that these anatomic and metabolic findings are not the same in all persons, thus explaining the variability in response to opioids among patients. Thus, the "trial and error approach" has a scientific basis after all.

From Individualized Treatment of Sickle Cell Pain to Precision Medicine: A 40-Year Journey