Thursday, January 4, 2007
Pain recently published a tidy bit of research on opioid-receptor genetic polymorphisms and morphine for cancer pain. The study involved ~200 Norweigan cancer patients (most had advanced cancer) on morphine (chronically, but on stable doses) for their pain (mean dose 117mg/day; range 10-760mg/day). They ran genetic tests looking at polymorphisms of the mu opioid receptor OPRM1 and the catechol-O-methyl-transferase (COMT) gene (COMT is not an opioid receptor but is almost certainly involved in pain modulation), and analyzed to see if certain polymorphisms were associated with higher or lower morphine doses. They found that across this population certain COMT polymorphisms were associated with 60% higher morphine doses; certain OPRM1 were associated with nearly double the average morphine dose than other polymorphisms. In their multivariate analysis, the combination of two of the "low morphine dose" polymorphisms significantly predicted lower morphine dose.
It's important to note that mean pain scores were equal across the study & didn't vary based on which polymorphism you had.
A few things here... It's been long recognized that for reasons unclear some patients seem to require a lot more opioids than others to get adequate pain relief, and opioid receptor polymorphisms have been one of the top suspects as to why this happens. It's nice, however, to see supporting evidence for this in real-life cancer patients. There will be undoubtedly more research along this lines, and perhaps in the not too distant future we'll have some sort of DNA-array/chip diagnostic panel which will tell us something clinically helpful (take your pick: patient more/less likely to benefit from oxycodone vs. hydromorphone, patient likely to need higher doses of opioid so be prepared for a steeper dose escalation, etc. etc.). Who knows of course if this will actually pan out, as one assumes that there are many other factors affecting a patient's therapeutic opioid dose. Until then, though, research like this is useful for our less opioid -friendly or -knowledgable colleagues who ummm, struggle, with appropriate opioid dosing--to reassure them there are authentic physiologic reasons why some people need "high" opioid doses.