Biomarkers May (or may not) Indicate Chronic Pain

Biomarkers May Indicate Chronic Pain, Aid Personalized Treatment – Pain Medicine News – by Kaitlin Sullivan – Apr 2020

People who suffer from chronic pain may have abnormal levels of 11 biomarkers related to metabolites and nutrient deficiencies, according to a retrospective observational study published in Pain Physician (2020;23[1]:E41-E49).

Although the research is still in its early phase, these findings provide a snapshot of physiologic abnormalities found in a subset of patients with chronic pain.

“Subset” is the critical word here. If these “abnormalities” aren’t found in ALL patients with pain, how can they be used as “biomarkers” for pain?

For the novel study, researchers analyzed the results of 17,834 tested unique urine samples collected from chronic pain patients in clinics between July and December 2018.

The researchers tested each sample for abnormal levels of biomarkers that indicate

  • systemic inflammation,
  • oxidative stress,
  • neurotransmitter turnover and
  • micronutrient status

conditions that past research has linked to chronic pain—and found that 77% of patients had at least one of them.

Of these patients,

  • 29% had elevated levels of quinolinic acid;
  • 21% had elevated levels of the acrolein metabolite 3-hydroxypropyl mercapturic acid;
  • 19% had elevated pyroglutamate, a biomarker indicating glutathione depletion; and
  • 17% had elevated xanthurenic acid, which is linked to vitamin B6 deficiency.
  • Just 10% had elevated methylmalonic acid, a sign of vitamin B12 deficiency, and
  • 8% had abnormally low levels of neurotransmitter metabolites.

A Measurable Pain Scale

Unlike existing pain scales that rely on patients’ perception of their own pain, future research on abnormal biomarker measurements could provide hard data for pain tests.

Yes, but… the results of any brain scan can only be compared to others from the same individual because our brains can be as different as our bodies. And they have no idea if these biomarkers contribute to pain or are the result of pain or if changes in these biomarkers will lead to changes in pain levels or vice versa.

They are clearly looking for a “pain meter” so they can “know” how much pain we are in instead of having to take our word for it. In what other areas of medicine do we insist that a patient’s report be verified by measurable data rather than believing it?

When a patient is taking an anti-itch medication, the doctor asks if they itch less and simply believes what the patient says. When a patient is taking antidepressants, the doctor asks if they are less depressed and then believes their answer. If a person is taking blood thinners or statins and reports side effects, they are believed and different blood thinners or statins will be trialed.

In the normal “practice of medicine”, doctors don’t just take medication away without an effective substitute. The patient’s feedback is not doubted and the doctor works with them to find other medications/treatment alternatives that accomplish the same function.

Predicting Outcomes

In fact, previous studies estimate that just 30% of chronic pain is effectively treated with analgesics (Discov Med 2011;11[58]:197-207).

Despite the soaring costs of treating chronic pain, complete relief is uncommon due to a limited number of current treatments,

What’s really preventing relief is the drug war’s fixation on our prescription medication. And then there’s the ineffable complexity of pain itself. Is it a sensation? a perception? an idea?

Dr. Martucci also said although it is unlikely one singular biomarker will ever be linked to chronic pain, an inexpensive urine test like the one in this study that tests for a range of abnormal biomarkers could be used in addition to other tests—including neuroimaging, and blood and genetic analysis—to provide more personalized therapies.

Correcting Underlying Issues

For the next phase of their research, the team plans to conduct a small, prospective, multicenter study based on intervention, Dr. Deer said. Doctors will use vitamins, diet and lifestyle changes, such as quitting smoking, to correct these biomarkers in patients, and then measure how these changes affect chronic pain.

If the intervention is successful, pain may be managed in some patients using personalized nutritional therapies instead of opioids, he said.

Some Study Limitations

This study did not account for the role that medications or conditions other than chronic pain could have played in these abnormal biomarkers.

In addition, Dr. Martucci said the next phase of research should use subgrouping to link specific biomarkers to specific types of chronic pain.

“Subgrouping within this data set would give us information about what these differences really mean,” Dr. Martucci told Pain Medicine News. “We don’t want to overemphasize what is actually being done in this study.

Well, that’s certainly not what it looks like. The first part of the article gave lots of data about the various biomarkers they found, but I had to read until the very last part of the article to find the following reality-check:

It’s the discovery of biomarkers, and the one that showed the most difference was only different in 29% of the patients.”

After all that information about the various biomarkers and how they might be related to underlying pain, they invalidate a big part of their own study by mentioning that those markers only show significant differences in 30% of pain patients.

To me, this makes the whole study almost pointless. If their findings only apply to one-third of pain patients, these biomarkers are clearly not going to be useful for detecting pain.

Other researchers have tried to determine a “pain meter” from brain imaging but suffer from the same fundamental problem. Comparing brain scans from different individuals can show differences unrelated to pain.

Other thoughts?

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