The sensation of pain is a subjective feeling that can vary between individuals but has objective roots, tied to a profound evolutionary response. Pain reflects damage to the organism, both real and perceived. In fact, the individual’s mental state can significantly affect their perception of pain, with psychiatric patients often exhibiting an increased perception of pain. As such, accurately diagnosing pain has proven difficult, leading to the use of drugs, such as opioids, more often than not to simply manage it.
Current diagnostic tests for diagnosing pain
There have been a number of diagnostic tests designed to help find the cause of pain, though it has proven difficult to diagnose pain, especially chronic pain, using labs and diagnostic tests. This generally means that arriving at a diagnosis is often a long process. This is partly due to the multi-faceted root cause, which involves the interaction of the nervous system and the brain, and can also involve a physical cause as well as emotional components. While no one test for pain exists, diagnosing pain can be done through imaging and nerve tests. Some of the most common imaging tests currently used are:
- X-Ray: Radiography is used to examine a patient’s skeletal system and look for any abnormalities. One of the most common sources of pain tied to bones is osteoarthritis. This can especially be a prominent issue in the knees and other joints.
- CT Scan: Compound tomography is used to image soft tissue, in addition to bones. This can be used to see herniated discs and determine if it’s impinging on a spinal nerve or the spinal cord.
- MRI: Magnetic resonance imaging uses magnetic fields to produce high-resolution images of bones and soft tissue. An MRI can determine if lower back pain is caused by more than simply muscle strain and corroborate findings obtained from a neurological examination, including potential nerve damage.
The cause of a patient’s pain may not be readily apparent in these imaging scans. As such, nerve tests may also be conducted to determine the functionality of the nervous system.
- Electromyography: This test measures the response of muscles to nerve signals. If the nerves have been damaged in any way, the muscles will not respond well, indicating that they may not be receiving clear messages.
- Nerve Conduction Velocity: This nerve test determines the velocity at which signals travel along the nerves. Slowed signals are a clear sign of damaged nerves.
- Quantitative Sensory Testing: This encompasses a couple of different tests. It can assess how well a patient responds to various sensory stimuli, such as pain and temperature changes.
Certain cases will also require that blood tests be performed. This can be used to detect diseases that may cause pain, such as rheumatoid arthritis, or to verify the levels of inflammation in the body. In addition, a recent research article has stipulated that they have developed a “prototype for a blood test that can objectively tell doctors if the patient is in pain, and how severe that pain is”.1
New diagnostic biomarkers
Given the subjective nature of pain, clinicians have been looking for a more objective measure of pain that they could use to diagnose patients accurately. This has led various researchers to investigate if they can identify certain biomarkers of pain in the blood that can then be used to determine if a patient is in pain, as well as the likely severity. These studies typically involve large cohorts that analyze the gene expression profiles of patients with self-reported low-pain and high-pain states.1
Biomarkers have emerged as essential tools in various disorders where subjective self-reporting has proven unreliable. The use of biomarkers in diagnosing pain is further supported by the fact that typically tissue biopsies of the brain or spinal centers are not possible.1 Blood biomarkers, which are far more accessible, can act as a “liquid biopsy”. By analyzing gene expression in these patients, researchers can determine a multitude of genetic variants and environmental effects that may cause pain. This includes biomarkers with increased expression (putative risk genes) and decreased expression (protective genes).
Some of the new diagnostic biomarkers determined to date that are believed to be correlated with pain are MFAP3, GNG7, CNTN1, LY9, CCDC144B, and GBP1. GNG7 (G protein subunit gamma 7) was found to be a strong predictor of future pain-related emergency visits, while CNTN1 (contactin-1) was more related to pain intensity, with high pain associated with decreased gene expression, indicating CNTN1 is a pain suppressor gene. Most biomarkers showed universal function, regardless of gender or diagnosis. However, certain genes showed a greater correlation in a specific gender. For example, CNTN1 was linked to chronic pain in women, while LY9 (lymphocyte antigen 9) and MFAP3 (microfibril-associated glycoprotein 3) were linked to post-traumatic stress disorder (PTSD) in men. Some of the individual biomarkers identified are already targets of existing drug treatments.
Opioid prescriptions and chronic pain
The use of biomarkers for diagnosing pain in a patient, as well as the severity, will allow physicians to provide treatment in a more objective, quantifiable manner. The over-prescription of pain medication, specifically opioids, was partly due to the fact that there was no objective measure of whether someone was in pain or how severe their pain was.1 Once a patient complained of being in pain, they would simply be prescribed opioids to alleviate the symptoms. Instead, biomarkers may help personalize pain treatment. Certain biomarker profiles can be matched with specific drug treatments, as well as natural compounds, improving patient outcomes and eliminating the associated dependency that comes with opioid use.
Many of the identified biomarkers already have a non-opioid compound identified as a treatment option, including some that have been used for decades to treat other things. This will allow physicians to prescribe medicine that is more appropriate to the individual person, optimizing the good a drug can do while also minimizing its potential harm. This also increases the options available to physicians and eliminates the one-size-fits-all approach that led to the opioid crisis.
Furthermore, the biomarkers can also help predict if someone is exhibiting chronic, long-term pain, which might result in future emergency room visits. With biomarkers already identified that are more prevalent in men or women, researchers hope that further biomarkers can be identified that can be linked to specific causes of pain, such as headaches, migraines, fibromyalgia, and so on.
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- Towards precision medicine for pain: diagnostic biomarkers and repurposed drugs. A. B. Niculescu, H. Le-Niculescu, D. F. Levey, K. Roseberry, K. C. Soe, J. Rogers, F. Khan, T. Jones, S. Judd, M. A. McCormick, A. R. Wessel, A. Williams, S. M. Kurian, F. A. White. Molecular Psychiatry (2019) 24:501–522