Building Solutions to Chronic Pain Through Clinical Research

Anyone who has worked in or lives near a construction site knows the backup sound of trucks. That high-pitched, excruciatingly loud beeeep, beeeep seems to be almost constant during construction projects. Although annoying, it’s an important sound; it alerts workers and bystanders to potential danger as huge vehicles with limited visibility move around. However, when the construction lasts too long, the constant beeeep both fails to elicit an appropriate caution response and drives you a bit nuts.

Normally, pain is like the beeeep from your body; it tells you to Watch Out! and move away from danger. Pain is a critical signal, protecting both tissue and people from being damaged or destroyed.^[1] How pain works is quite complex. Special receptors called nociceptors sense a change that might be dangerous: excessive skin stretching, hazardous chemicals, or very high or low temperatures.^[2,3] When a harmful  change occurs, nociceptive cells transmit a signal to the spinal cord, where the signal is interpreted and may be sent to the brain.^[2,3] In the brain, these signals are just one of many inputs contributing to the complex psychological experience we perceive as pain.^[4] Think back to the construction site; if you’re wearing earmuffs or are sitting inside a heavy building with solid walls, the signal might not be perceived as loud - or at all.

Pain is useful, but when we experience it constantly and in the absence of danger, it can be like a wrecking ball on your mind. Chronic pain is pain in the absence of damage for 3 or more months.^[5,6] It is very common, affecting around 20% of American adults; around 50 million people in this country alone.^[6] Around 1 in 15 Americans experience high-impact pain that affects daily life and work activities.^[6] Observational studies show that American Indian/Alaskan Native people, bisexual people, women, and those who are divorced or separated are at higher risk for developing chronic pain.^[6] The chances decrease with wealth and education level, but the most significant factor is age, with older people at much higher risk of chronic pain than young people.^[6] 

Pain is a complex condition and very few cases of chronic pain originate from a single cause; most are a combination of biological, psychological, and social factors.^[5] Chronic pain may still be said to originate from an initial injury, a disease like diabetes or osteoarthritis, other body sources like inflammation, or from changes to the neurons or brain components involved in experiencing pain.^[1,2,5,7] Regardless of the “cause” of pain, acute (short-term) and chronic pain are fundamentally different from each other.^[1] Acute pain is the normal nociceptive response to damage or a threat of damage. Chronic pain results in changes to cells, receptors, emotions, cognitive functions, cell circuits, and how cells talk to each other.^[1,7] Ultimately, the experience of chronic pain is the change from experiencing external injury to an internal state of pain.^[7]

Biologically, the way chronic pain manifests can be lumped into three categories: constant nociceptive input, neuropathy, and mixed pain. Constant nociceptive input is like a dump truck’s backup alarm getting stuck and constantly beeping. The truck isn’t moving, so there’s no danger, but the signal continually sounds. This is typical of conditions like osteoarthritis, but there are many ways it could happen. Even with our simple dump truck example, there are myriad possible reasons the alarm might sound: someone might have left the truck on, the beeping mechanism might be broken, the electrical system might be on the fritz, someone could be playing a prank, etc. Neuropathic pain is like hearing a ringing in the ears from hearing damage even after the beeping has stopped. With neuropathy, the neurons that carry or interpret pain signals are damaged and imbalances of pain pathways are interpreted as pain in the brain.^[1] Mixed pain is a combination of the two, with things like low back pain combining constant nociceptive input and nerve damage. Regardless of the nature of pain, complications of chronic pain are severe and include decreased quality of life, depression, substance abuse, increased chance of dementia, and suicide.^[6]

So what can we do about chronic pain? Unfortunately, chronic pain is a severely undertreated condition and many people struggle to find treatments they can tolerate.^[2,5] Current prescription medications include tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors (SNRIs), opioids, gabapentinoids, ion channel blockers like the newly approved Journavx (suzetrigine), and topical creams or ointments.^[2] These approved medications target various channels, receptors, and systems associated with our experience of pain, but come with side effects and are limited in the types of pain they are designed to treat.^[2] With 20% or more of American adults continuing to live with chronic pain, there is a clear need for new treatments that target new systems.^[5,6] Some possible targets include growth factors that affect neuron signals, inflammation receptors, new ion channel receptors, medications that target the spinal cord, and others.^[2] With the help of randomized, controlled clinical trials, we may be able to construct new treatments and build a future where chronic pain fades away like the sweet hum of the last dump truck driving off a construction site.

Creative Director Benton Lowey-Ball, BS, BFA

As of publication, a pain research study is coming soon to Flourish Research - Merritt Island. Please call them for details and mention that MedEvidence sent you.

Flourish Research - Merritt Island (321) 221-0224

References:

^[1] Kuner, R., & Flor, H. (2017). Structural plasticity and reorganisation in chronic pain. Nature Reviews Neuroscience, 18(1), 20-30. https://www.nature.com/articles/nrn.2016.162

^[2] Borges, J. P., Mekhail, K., Fairn, G. D., Antonescu, C. N., & Steinberg, B. E. (2021). Modulation of pathological pain by epidermal growth factor receptor. Frontiers in Pharmacology, 12, 642820. https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.642820/full

^[3] Kandel, E. R., Schwartz, J. H., Jessell, T. M., Siegelbaum, S., Hudspeth, A. J., & Mack, S. (Eds.). (2000). Principles of neural science (Vol. 4, pp. 1149-1159, 1227-1246). New York: McGraw-hill.

^[4] Johnson, M. I. (2019). The landscape of chronic pain: broader perspectives. Medicina, 55(5), 182. https://www.mdpi.com/1648-9144/55/5/182

^[5] Knopp, K. L., Downing, A. M., Anthony, L., Chaterjee, S., Price, K., & Sparks, J. (2024). An innovative phase 2 chronic pain master protocol design to assess novel mechanisms in multiple pain types. Pain Reports, 9(6), e1203.https://pmc.ncbi.nlm.nih.gov/articles/PMC11487222/

^[6] Rikard, S. M. (2023). Chronic pain among adults—United States, 2019–2021. MMWR. Morbidity and Mortality Weekly Report, 72. https://pmc.ncbi.nlm.nih.gov/articles/PMC10121254/