Why haven’t we cured chronic pain?

February 5th, 2023

Written by: Lindsay Ejoh

Chronic pain is a staggering health crisis that negatively impacts the lives of 1 in 5 Americans and millions more around the world. It is defined as pain felt after the usual recovery period from an injury or pain experienced alongside a chronic disease¹. Despite its prevalence and billions of research dollars spent per year to understand and treat chronic pain, we do not yet have a cure, or a permanent and reliable treatment for a disorder. Because it can feel hopeless to have or witness a condition that has no cure, and not know how close scientists are to finding one, in this post I will highlight three challenges researchers face in developing a cure for chronic pain.

1. It is difficult to accurately measure pain.

To determine if a medical intervention can successfully treat a disorder, it is important to be able to reliably measure symptoms of that disorder. Pain is such a subjective experience that it can be difficult to measure. Let me prove it to you: pinch yourself as hard as you can, wait 30 seconds, then pinch yourself with just enough pressure to feel pain but not enough for it to sting too badly. Can you rate your pain levels from each pinch from 1-10? Doctors often ask patients to similarly rate their pain across a scale, either providing a range of numbers or using a set of pictures that illustrate a range of pain levels, called a Visual Analog Scale (Fig. 1). Though these can be useful for quickly determining one’s pain levels, these scores can be biased and depend on the context². For example, patients may report higher pain levels if they are worried that their provider might not respond to their complaints. On the other hand, patients may report lower pain levels if they’re concerned about how their pain will be perceived by others or when concerned about the expenses associated with pain treatment.

Additionally, there are structural issues in healthcare that lead to doctors often not believing patients when they report pain levels³. A 2016 study showed that 40% of surveyed medical students believed that “black people have thicker skin and less nerve endings that white people” and therefore experience less pain. This myth has been disproven, but many of these biases still hold today across different demographics, making it even more difficult to accurately assess patients’ pain.

Oftentimes, conditions and diseases are diagnosed with the help of biomarkers⁴, which are measurements of bodily processes that can indicate abnormalities or disorders. For a biomarker to be clinically useful, it must be specific to that disorder and easily measured by providers in many different types of healthcare facilities.

There is a lack of accurate and consistent biomarkers to detect chronic pain. Doctors have explored some biomarkers for chronic pain by measuring brain and nerve activity, taking structural brain scans, and even testing for the presence of certain compounds in bodily fluids, yet these methods can be flawed⁵. Often, a biomarker that can accurately diagnose chronic pain in one individual does not work in another. Adding to these challenges, many of the proposed biomarkers of chronic pain can be detected in patients who are not experiencing chronic pain, making them unreliable detectors of chronic pain. There’s no reliable or consistent compound in the blood or stool we can test for to confirm that someone has chronic pain.

2. Chronic pain disorders have different causes.

Many times, we look for cures for certain diseases by eliminating what causes the disease in the first place. However, it is impossible to attack chronic pain at its roots because different chronic pain disorders have different origins. Some are caused by injury or amputation, but others seem to appear out of nowhere. For example, one study showed that 1/3 of youth with muscle/bone pain don’t report a root event ⁶. I personally have had chronic shoulder pain since 2016 with no memory of how it started. There is no one-size-fits-all cause for chronic pain.

Many people with chronic pain experience extreme discomfort in specific parts of their bodies, yet when doctors run tests, there is no evidence of injury in those areas. These are called functional pain syndromes^7,8, in which pain exists without a detectable injury. Some examples of these include fibromyalgia, chronic migraines, and irritable bowel syndrome. This becomes even trickier for treatment because it’s difficult to cure what we can’t even see.

3. The pain drugs we have are flawed and come with unpleasant side effects.

To treat chronic pain in humans, we often use drugs, which can come with harmful side effects. For example, opiates like oxycodone, heroin, and fentanyl are very effective at shutting down pain cells in the body and brain, but they also act on addiction centers and shut down muscles necessary for breathing at higher doses¹¹. Anti-inflammatory agents that can treat pain, like ibuprofen, often lead to stomach issues with long-term use¹². Acid reducers that are often prescribed for inflammatory bowel syndrome have negative long-term effects like increased risk of heart attack, bone fracture, or stomach cancer¹³. Additionally, a lot of these drugs don’t work on everybody because chronic pain presents differently in different people- even those with the same disorder.

Since pain is a conscious experience generated by the brain, we can alter the experience of pain by manipulating the brain’s activity. We have been able to “cure” several different types of chronic pain in mice^9,10 this way, by changing the activity of neurons in different parts of the brain and body that we know are involved in pain processing. However effective, these tools are very invasive and reduce the lifespan, so they are not ready for human use.

What does the future of chronic pain treatment look like?

Since we can use gene-editing technology to specifically target pain cells, we can more easily relieve mice’s chronic pain symptoms. However, we cannot genetically engineer humans, so scientists are developing tools like deep brain stimulation to alter brain activity on a broader scale to help treat human chronic pain.

Alternatively, many people use psychological therapies like mindfulness meditation, cognitive behavioral therapy, pain reprocessing therapy, and hypnosis to treat their pain. Often, patients report a better relationship with their pain and better quality of life from these methods, though they do not consistently or reliably work on everyone.

Right now, no treatment is perfect, and it may take several tries to find the right method for each individual. Pain researchers have a lot of open questions to answer and hurdles to climb in uncovering the origins of chronic pain disorders, diagnosing, and measuring pain, and developing therapies with minimal side effects. However, the payoff will be extraordinary as researchers trudge forward to treat the millions of people around the world who deal with unmanageable chronic pain disorders.

References

1.         Jackson, T. P., Stabile, V. S. & McQueen, K. A. K. The Global Burden Of Chronic Pain. ASA Newsletter 78, 24–27 (2014).

2.         Boring, B. L., Walsh, K. T., Nanavaty, N., Ng, B. W. & Mathur, V. A. How and Why Patient Concerns Influence Pain Reporting: A Qualitative Analysis of Personal Accounts and Perceptions of Others’ Use of Numerical Pain Scales. Frontiers in Psychology 12, (2021).

3.         Hoffman, K. M., Trawalter, S., Axt, J. R. & Oliver, M. N. Racial bias in pain assessment and treatment recommendations, and false beliefs about biological differences between blacks and whites. Proc Natl Acad Sci U S A 113, 4296–4301 (2016).

4.         Strimbu, K. & Tavel, J. A. What are Biomarkers? Curr Opin HIV AIDS 5, 463–466 (2010).

5.         Eldabe, S., Obara, I., Panwar, C. & Caraway, D. Biomarkers for Chronic Pain: Significance and Summary of Recent Advances. Pain Res Manag 2022, 1940906 (2022).

6.         Becker, A. J., Heathcote, L. C., Timmers, I. & Simons, L. E. Precipitating events in child and adolescent chronic musculoskeletal pain. Pain Rep 3, e665 (2018).

7.         Clouse, R. E. et al. Functional Abdominal Pain Syndrome. Gastroenterology 130, 1492–1497 (2006).

8.         Crabtree, D. & Ganty, P. Common functional pain syndromes. BJA Education 16, 334–340 (2016).

9.         Najjar, S. A. et al. Optogenetic inhibition of colon epithelium reduces hypersensitivity in a mouse model of inflammatory bowel disease. Pain 162, 1126–1134 (2021).

10.      Corder, G. et al. An amygdalar neural ensemble that encodes the unpleasantness of pain. Science 363, 276–281 (2019).

11.       Kimmey, B. A., McCall, N. M., Wooldridge, L. M., Satterthwaite, T. D. & Corder, G. Engaging endogenous opioid circuits in pain affective processes. J Neurosci Res 100, 66–98 (2022).

12.      Ngo, V. T. H. & Bajaj, T. Ibuprofen. in StatPearls (StatPearls Publishing, Treasure Island (FL), 2024).

13.      Yibirin, M., De Oliveira, D., Valera, R., Plitt, A. E. & Lutgen, S. Adverse Effects Associated with Proton Pump Inhibitor Use. Cureus 13, e12759.

Cover photo by Roberto Sorin on Unsplash. 

Figure 1 by Robert Weis on Wikimedia Commons.