The Path to Chronic Pain: Unraveling the Complex Causes (2 of 3 Pain Series)

The Path to Chronic Pain: Unraveling the Complex Causes

How does pain, usually a helpful sensation, turn into the unworkable problem we call chronic pain, affecting over a quarter of the world’s population? Chronic pain is a lingering and persistent sensory experience, but it’s far more complex than that. It emerges from interactions within our body’s systems, shaped by a mix of biological, psychological, social, and environmental factors. Over the last 50 years, advancements in evolutionary and complexity sciences have given us new ways to look at this frustrating human problem. In previous posts, we introduced evolution as the science of change, defined the nociceptive apparatus—our body’s internal harm detector—and explored how complexity science can help us better understand health and wellness. Now, we’re ready to explore this different perspective of pain.

The Nociceptive Apparatus: A Constantly Adapting System

Our body’s harm detector, the nociceptive apparatus, has evolved to help us survive by quickly sensing when we’re injured or might get injured. This system can become more sensitive when needed, which is helpful to avoid further harm.

For example, if you step on something sharp, your harm detector might become more sensitive, increasing its responsiveness to detect additional potential injuries. It does this through multiple processes of change, including making changes in the spinal cord (part of the connecting pathways of the harm detector), allowing it to receive more information from nearby nerves. As a result, the harm detector starts picking up signals from nerves not typically involved in sensing harm, like those for light touch, gentle pressure, or blood flow. At the same time, the brain sends signals and chemicals that can speed up or slow down how these messages travel through the spinal cord. These processes are technically called peripheral and central sensitization. 

Along with these changes, the harm detector undergoes structural and functional changes That’s why we look at the harm detector from 3 levels: local, long, and global. These levels reflect the changes happening throughout the body in response to actual or potential injury. This process can lead to a phenomenon called allodynia, where things that usually aren’t painful, like a light touch, are suddenly experienced as painful.

While this increased sensitivity helps with survival, it can cause problems when it happens too often and doesn’t return to normal. This is an example of progressive change in a complex system, like the harm detector within the body’s ecosystem. Over time, small changes can accumulate and reach a tipping point, at which one final change causes the system to enter a completely different state. This new state is known as a Complex Maladaptive System (CMS) in complexity sciences.

To understand how this happens, it’s essential to know that the body’s harm detector, like everything else in the body, is constantly changing and adapting to its environment. Let’s take a look at how these changes can develop over time.

How the body’s ecosystem primes the harm detector for change

Increasingly, scientific research highlights the complex interactions between the nervous, immune, and endocrine systems in developing chronic pain and other health conditions. Together, these interrelated systems are seen as the neuroendocrine-immune (NEI) axis, which I often call the ‘holy trinity’ of survival. The nervous system triggers rapid responses such as sensory awareness, movement, and changes in position. For example, when you quickly pull your hand away from a hot object, the harm detector plays a vital role in this process. The immune system fights infections and manages processes like cell breakdown and generation. The endocrine system, together with the autonomic nervous system, controls the body’s stress response—fight, flight, or freeze—by releasing chemicals in the form of hormones and neurotransmitters, such as cortisol and catecholamines (like adrenaline). These chemicals help prepare the body for real or perceived harm, such as in stressful or threatening situations. They do this by raising heart rate, directing blood flow to vital organs, and exciting the nervous system to enhance our ability to see, hear, feel, and move faster. These chemicals and interactions with the nervous system are essential for survival.

While this system evolved to handle immediate threats like encountering a lion, our advanced ability to think, predict, and analyze has introduced internal threats. This complex thinking relies on language, which not only helps us communicate but also enables us to form internal symbols. These symbols allow us to troubleshoot and assess potential dangers—whether they come from past experiences or imagined future scenarios. This ability can trigger the same stress responses as real physical dangers, leading to feelings like worry, fear, anxiety, or anger, all of which are meant to protect us—not just from physical harm, but also from social threats involving strangers or relationships with friends, family, and work.

However, if these stress responses are activated too often or for too long, the body adapts by making them easier to occur, even in less threatening situations. These changes don’t happen in isolation; they involve many systems in the body, including the harm detector.

Local changes to the harm detector

As we previously described, our harm detector is a physical part of the nervous system made up of specialized nerves. These nerves have sensors, called ion channels, that respond to stimulation from their surroundings. Interestingly, these ion channels have a surprisingly short lifespan—some lasting only 3 hours, while most survive up to 3 days—before they are replaced. Our genetic code, which acts like a long-term blueprint we inherit, gives a basic template for this. However, our epigenetic code, influenced by our environment and can change during our lifetime, helps determine what kind of sensor will replace the old one. There are over 300 types of sensors that we have classified scientifically so far (likely more for us to find!). But for simplicity, we can categorize nerve sensors into the following categories:

• Mechanical: Sensors that respond to physical changes like pressure or stretch.
• Chemical: Sensors activated by chemical substances, often in response to inflammation or stress chemicals.
• Blood Flow: Sensors that detect changes in blood flow, which can indicate underlying supply issues.

Figure 1 – Nerve Fibers and Nerve Sensors

These local changes occur alongside global-level changes in the harm detector, depending on what’s happening inside our body and the world around us. As a result, the harm detector is constantly adapting to the current state of the body’s ecosystem. If the body regularly releases chemicals from the endocrine and immune systems that make the nerves more sensitive, the types of sensors will likely change over time. The sensors on the nerves may adjust to better match the environment. For example, if the body constantly reacts to potential threats—whether internal or external—the entire system, including the harm detector, will adapt and become more sensitive due to the increased levels of chemicals in the bloodstream. These changes don’t stop at the local and global levels; we must also account for changes in the connecting pathways of the body’s harm detector.

How Connecting Pathways Evolve in the Development of Chronic Pain

The connecting pathways of our body’s harm detector consist of long nerves (like the sciatic nerve), the spinal cord, and the brain. In the spinal cord, signals related to potential harm are sorted by “sorting workers,” known as Wide Dynamic Range (WDR) neurons, and “bouncers,” called interneurons. The sorting workers determine how many signals are sent to the brain based on the number of signals they receive. If they’re overwhelmed with signals, they let more through. The bouncers control which signals make it through and adjust based on instructions from the brain or body. Over time, if this system becomes overly sensitive, more signals related to harm detection are sent to the brain. Although we don’t fully understand why, MRI scans show that, over time, continuous harm detection signaling can lead to inflammation in the spinal cord and brain, in addition to biological changes in the nervous system. Some of this inflammation may be caused by the immune system responding to actual or potentially dangerous invaders. However, some inflammation comes directly from the nerves themselves through a process called neurogenic inflammation. This occurs when nerves release chemicals that cause inflammation, swelling, and irritation. As immune and/or neurogenic inflammation builds up, the body’s harm detection system becomes more sensitive. It may also activate the harm detector directly, responding to minor triggers as if they were more serious. This increased sensitivity can eventually push the system to a tipping point, where signals from the harm detector shift from being adaptive and helpful to maladaptive and unhelpful.

From Adaptive to Maladaptive: The Shift to Chronic Pain

Initially, the body’s harm detector adapts to protect us from injury. For example, after a back strain, it may become more sensitive to ensure potential harm is noticed. However, if the body has experienced long-term activation of the harm detector across multiple levels, this new injury could trigger a tipping point.

In complexity science, a tipping point is when small changes accumulate, leading to a dramatic shift in how a system operates. In this case, the harm detector may become overly sensitive, reacting to harmless stimulation as if it were an injury. This heightened sensitivity starts locally at the injury site but doesn’t remain confined there. It spreads across the connecting pathways and global levels of nociceptive apparatus. If the body is continually exposed to stress, inflammation, or other biological threats, the nociceptive apparatus may send harm detection signals even when no actual injury is present. These changes involve local-level adjustments and broader shifts across the neuroendocrine-immune axis of the body.

When these mechanisms stay active for too long, they may shift from being useful to harmful. This tipping point transforms the system from a Complex Adaptive System (CAS)—which is flexible and responsive—into a more rigid unworkable Complex Maladaptive System (CMS). In this state, the harm detector becomes locked in overdrive, potentially contributing to the development of chronic pain. In this context, chronic pain is no longer a helpful warning of immediate harm but rather a sign of a system stuck in an unworkable state. This understanding highlights the benefit of viewing pain as an emergent phenomenon shaped by complex interactions within the body’s systems. Over time, these interactions can become maladaptive, possibly leading to chronic pain and functioning as a CMS. Moreover, beyond affecting a single area, these widespread changes within the body’s ecosystem and nociceptive apparatus can spread to other parts of the body, leading to a more widespread experience of chronic pain and the development of other symptoms.

Up Next: How Lifelong and Generational Changes Shape Our Experience

As we’ve seen, chronic pain is shaped by complex changes in the body’s harm detection system. While these changes can be helpful for survival, they can also lead to long-term sensitivity and maladaptation, creating persistent experience of pain that is felt throughout the body.

In the next blog, we’ll further explore how these changes can evolve over a lifetime, influenced by factors like adverse childhood events (ACEs), social determinants of health (SDOH), trauma (such as what has been called PTSD), and other environmental pressures. We’ll look at how our genetic makeup and life experiences shape chronic pain and even how these effects can be passed across generations. This deeper understanding offers new insights into working with pain for ourselves and future generations. Stay tuned for a closer look at how evolutionary science helps explain the cycle of chronic pain and its lasting impact on families and communities.