We’ve spent much of this series discussing things that are mostly within our control: nutrition, mindset, participation in our healing etc. It turns out that for many of the common chronic pain conditions (like #migraine and chronic low back pain), 50% of your pain may be related to genetics. Now, we all know that even though genetics may increase risk, it’s our lifestyle choices that actually turn on the good genes and turn off the bad genes. So, do you know if you’re living within the context of your evolutionary needs? Might your pain be related to some combination of genetics and lifestyle? What is that combination for YOU?

Fibromyalgia

Studies show that fibromyalgia (FM) has 50% heritability, meaning it is in part passed down through our genetics. One of the signs of FM is low levels of the neurotransmitter serotonin in the blood and cerebrospinal fluid, which is also found in other disorders like anxiety and depression. It turns out that people with a defect in a gene called SLC6A4 (which is involved in moving that all-important serotonin molecule around the nervous system) might have a higher risk of all of these conditions. The thing is, though, people with fibromyalgia are often prescribed anti-depressants that in theory increase brain levels of these chemicals. While anti-depressants like SSRIs do have a time and place, they fail to get to the root of dysfunction within our brains that are far too complex to solve with just one simple medication.

So, what can be done? Well, it’s important to understand whether you’ve got this genetic mutation that impacts your risk. If so, substances like Curcumin and Bacopa are able to up regulate the gene to make it function more effectively. Just like with SSRIs, though, this alone is not enough. Understanding what else might be contributing to low serotonin is crucial. How is your gut function? How is your sleep? Is your body inflamed? Are you socially connected to people who “get you”?

That last one is important. In one study (PMID: 25910391) adolescents who had the “risky” version of the SLC6A4 gene were indeed at higher risk of conditions like depression and perceived loneliness. The good news is that adequate parental support early in life blocked the negative impact of this gene, helping these kids to feel less lonely and less depressed. Your genes are not your destiny, but knowing your unique susceptibility is important.

Though more research is needed, many other genes may play a role. Just a few to consider with possible FM:

- COMT-Val15Met (rs4680)

- COMT-Vall5Met (rs4818) and (rs4633)

- DRD4

- MAO-A

- GTPCH

- GABRB3

- Sodium channel NaV1.7 (SCN9A)

- APOE

- MYT1L

- NRXN3

- MTHFR C677T

Has anyone talked to you about how to pain-proof yourself through an understanding of your genetics? Find a healthcare provider who understands this stuff.

Source: PMID: 23545734, 23280346

Opioids

The #opioidepidemic has gotten so much press in the last few years that’s people have become de-sensitized to the real stories of suffering that it’s caused. That’s ironic, of course, given the role that opioids have played in helping people to feel less sensitive to their pain. This is a group of people, with legitimate chronic pain, that’s been under appreciated and in some ways forgotten as a result of national and state-wide efforts to resolve the challenges we face with opioid abuse.

As with all things in medicine, one size simply does not fit all. Appropriate treatment for both opioid abuse and chronic pain must be comprehensive, taking into account the individual needs of each patient. One such way to individualize care is to base it on genetic risk, which helps us to approximate the likelihood that opioid medications will help someone with pain while assessing the probability of addiction. Still, many years after the human genome was mapped, this is an imperfect science. What we do know, though, is that looking at genetic risk can help us to personalize care. So, a few facts about the best studied gene in this regard, the mu opioid receptor gene (OPRM1, rs 1799971 to be specific) :

- In men, the presence of the “G” variant of this gene explains up to 4.7% of the difference in pain intensity for men with low back pain followed for 5 years. That’s a lot for just one factor of the many that contribute to pain (PMID: 28471875)

- Across 5 of the most common addictive substances, this gene increased risk of addiction based on a large meta-analysis looking at 28,000 people of European ancestry (PMID: 26392368)

- In a study of 207 people, those receiving morphine who had this “G” allele required 93% more of the drug for pain relief

- A just-published study of 450 people (mostly elderly women) found that this gene increases pain generated by nerves more than other genes studied (PMID: 31269327)

Is your doctor looking at genetics before coming up with YOUR treatment recommendations?

Post-Surgical Pain

Surgery can be incredibly scary. What’s worse is that it doesn’t always work and sometimes can even leave you in more pain than when you started. While surgery has an important role to play in the toolkit of the healthcare system when it comes to treating pain, it is more effective against the backdrop of comprehensive holistic care. When it comes to surgery for back pain, for example, the common understanding is that 1/3 of people get better, 1/3 of people stay approximately the same, and 1/3 actually end up feeling worse after the procedure.

While there are a lot of reasons for this, what’s true is that we tend to blame purely structural causes far too often. In fact, studies continue to show that when it comes to back pain, radiologists have a very hard time predicting who is in pain looking solely at issues with intervertebral discs and nerve damage on X-rays and MRIs.

Chronic post-surgical pain (CPSP) is another challenge that we have to deal with. Depending on the location of surgery, chronic pain that’s a direct result of the surgery has an incidence between 5% and 85%(!) (PMID: 18434337). It turns out that, like most things, there’s at least some genetic influence involved. A meta-analysis in the Journal of the American Pain Society of 21 trials found significant influence of the gene KCNS1 (rs734784) on post-surgical pain scores. It’s also been associated with lumbar back pain with disc herniation, higher phantom limb pain and stump pain in amputees, more severe sciatica pain before operation and higher sensitivity to experimental pain (PMID: 20724292). It’s believed that this gene impacts sensitivity to noxious (painful) stimuli and the nervous system activation that results from them.

There are many other factors involved, and all must be considered thoroughly. If you are considering surgery among your options, wouldn’t it be helpful to know your risk?

Source: PMID: 31129315

So far, we’ve been doing a quick survey of the role that your DNA may play in relation to chronic pain. The reality is that much of what we know has been discovered very recently, and most of the research we have isn’t ready for the “prime time” of clinical practice. When genetic information can guide clinical decisions, though, it can be quite helpful to have. One gene in particular continues to come up as a result of its involvement in how we perceive pain.

A group of researchers looked at several variants (rs6269, rs4633, rs4818, rs4680) of this gene to determine whether or not it predicted the likelihood that someone was feeling mild, moderate or severe pain, and then used this information to make treatment decisions including medication dosing. In particular, COMT status impacted how much of the opioid fentanyl participants needed 24 and 48 hours after surgery based on their pain levels (those with the “risk” variants consumed more of the drug). While this study was relatively small (92 people) and had no control group, the results were promising in that they indicated that genetics will likely play an important role in pain care in the not-too-distant future.

COMT is an interesting gene, with implications for things like mood, insomnia ADD/ADHD, Bipolar disorder, medication processing, and likelihood of successful placebo effect. Do you know your COMT status?

PMID: 25532715

Dr. Robert Kachko