Genetics and Pain: Optimizing Gene Expression and the Potential of Pharmacogenetics

More than 200 genes are involved in the processing of pain. And in recent years, research has been ramping up to better understand the genetics of pain.

“We have learned from twin studies that looked at migraine headaches, chronic low back pain and menstrual pain that genetics is a contributor to how we process pain,” says Pain Management specialist Teresa Dews, MD, who is leading Cleveland Clinic’s Pain Genomics Taskforce with Wilson Tang, PhD, of Cleveland Clinic’s Center for Clinical Genomics.

Dr. Dews says the influence of genetics on the pain experience ranges from 20 to 30 percent, but in some cases may be as high as a 60 percent influence. But just because a patient has a gene for a certain pain response, does not mean that the patient will experience the pain. There have to be environmental factors – this is called epigenetics – to trigger this pain response.

“A patient may have a group of genes associated with having more pain, but the patient can decrease their risk with good choices,” says Dr. Dews. “It’s about how people interact with their genes.” It’s important for patients to understand that genes are influenced by a person’s environment, including diet, toxins, chemical exposures, inflammation, stress and lack of sleep. Patients play a part in optimizing gene expression through their lifestyle choices.

Pharmacogenetics

It is pharmacogenomics testing that is providing information about how certain medicines are processed by an individual’s body. At this point in time, Dr. Dews says more work needs to be done to validate this testing. “There is so much variance in how people process many medications used for pain treatment. If you give pain medication to 10 patients, you will get the full range of pain relief from no impact at all to excellent pain relief,” says Dr. Dews. “Some patients are sensitive to medications. Others don’t respond well to medications. There are ultra-metabolizers to hypo metabolizers.”

How people metabolize medications comes down to how the body creates enzymes to process the medicine. She notes that there are patients who are resistant to pain meds, who want to know why nothing will work for them to stop the pain. Being able to distinguish which patients will be on either end of the spectrum could prove beneficial in coming up with the best medications to use for treatment. But the use of genetic testing for this purpose is still in its infancy. More research needs to be done to validate testing practices, and following this there will be barriers to making it a normal part of medical practice. The first being insurance coverage for these non-essential tests.

Patient demand

Today there are a lot of companies out there that are offering DNA testing direct to consumers. They say they can provide people with information on the type of metabolizer of medications, but there are very discreet things labs have to do to show that testing is valid and reproducible. People will find these companies on the web, but we have to question how valid the information is, Dr. Dews cautions.

“In my practice patients bring me a small pamphlet of their testing results and they tell me that they are a high metabolizer. If this is true, they may need to try another medicine as opposed to a higher dose of the same medicine,” says. Dr. Dews.

She goes on to say, “Historically, we have used trial and error and go from one medication to another until we find out what works. If genetics testing can help us better understand how a person metabolizes medications, it would improve our choices and perhaps decrease side effects and lack of benefit and help to identify drug-drug interactions.”

Dr. Dews says she can foresee a groundswell of requests from patients for pharmacogenetics testing. As with everything we do in medicine, Dr. Dews says it will come down to how we are using the information, if the patient can afford it and if they have access to it. “As a pain physician, I want to know what it will add to our ability to care for patients,” says Dr. Dews. “Do we need a fancy test to determine pain parameters or can we get this information from family history or how a patient has typically responded to medications in the past?”

Where she sees pharmacogenetics testing being most helpful may be in getting clues to whether a patient might be at risk for adverse effects from a type of medication, especially if they are not responding to more conservative treatments. It could enhance what physicians already know about their patients.

Looking to the future, one other area Dr. Dews says the Pain Genomics Taskforce would really like to have available is testing to find out which individuals are more prone to addiction. Currently, some companies say they can test for this, but this is not yet proven.

“The information we have on pharmacogenetics is preliminary with definite potential for helping to manage patients and decrease drug reactions,” says Dr. Dews. “But there is work to be done to translate the research at the bench and to find ways to apply it to clinical practice.”