Why Opioid Pain Relievers Don't Always Work

Most everyone knows narcotic pain killers like morphine, Percocet, and Vicodin are powerful. Doctors prescribe them with caution because although they relieve pain, they also have some nasty side effects. Addiction being one of those effects. But sometimes physicians are too cautious not realizing that some people require 10 to 40 times the standard dose to get the same effect.

Animal studies have confirmed what doctors see in the clinic -- there are some unique differences in patient responsiveness. Scientists have found that the wide variability in how people respond to these drugs might be genetic. And once they discovered this factor, they found more than one genetic trait that is involved.

For example, some folks don't have the CYP2D6 enzyme needed to activate the drug. Without this enzyme, the drug isn't metabolized (broken down) and the patient gets no (or very minimal) pain relief. Another problem occurs when P-glycoprotein doesn't function properly. This is the protein that transports the opioid across cell membranes. Without normal P-glycoprotein, there can be too little or too much opioid in the cells.

Here's one more example of genetic mutations that affect how opioids work in the human body. When the COMT gene is mutated, it no longer makes the enzymes that break down neurotransmitters that carry chemicals around the body. Without proper COMT, the cell receptor sites for opioid are also affected.

These examples are really only the tip of the iceberg. The more scientists explore this direction of research, the more differences in genetic makeup are discovered. The cell receptor sites just mentioned? It turns out there are probably many different types of pain receptor sites -- a change in any of these can affect how well opioids attach to the cell, transfer across the cell membrane, and have the intended effect to reduce pain messages.

Genetics isn't the only factor in how people respond to opioids. There is still a significant effect of personality and psychology -- some people tend to lean toward suffering rather than overcoming. And the source of the pain can also contribute to how well opioids work.

But for all we've learned about individual factors (including genetic variability), we are no closer to finding a successful treatment for pain. Scientists will continue to pursue genetic-guided pain therapy. It's likely that there are multiple genes involved and additional factors yet to be discovered. Finding the combination for each patient that prevents successful opioid use or in the opposite vein -- finding the combination of genetic (and other) factors that can lead to pain relief may become the next step in scientific discovery.

The vision experts in pain management suggest the future looks like this. Treatment will be personalized for each patient based on his or her individual genetic code. Their DNA will be examined with the information used to find the exact right drug that will be an effective pain reliever using the lowest dose possible. Even better yet, doctors will be able to take a blood sample and identify who is at risk for developing an addiction to specific opioids.

For now, it's helpful for health care providers to recognize and acknowledge that there are individual differences in how opioids work for different patients based on genetic variability. Just because someone doesn't get pain relief with the standard dose prescribed, doesn't mean they are addicted or becoming addicted. It could simply be an indication that they fall into that group of patients who need more (sometimes much more) of the same drug to get the same pain relief as someone who responds to the lowest dose possible.

Reference: 

Gabriel Miller. Genetics of Opioid Prescribing: Many Questions, Few Answers. In Pain Medicine News. February 2010. Vol. 8. No. 2. Pp. 1, 36, 39.

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