A Complex Systems Perspective on Pain

Chronic pain is a complex and confusing problem.

Unlike acute pain, which is well correlated with injury, chronic pain is often unrelated to tissue damage. It might be driven by a wide variety of factors like sleep, mood, thoughts, or emotions. And chronic pain is connected with other health problems like obesity, anxiety, depression, or IBS.

We can better understand the complexity of chronic pain, and its relationship to other multi-symptom disorders, by learning something about systems theory. I recently discovered two excellent papers which discuss pain and stress from a systems perspective. You can read full text versions of them here and here.

The basic idea is that chronic pain is often driven by dysregulation of a “supersystem” that coordinates defensive responses to injury. The supersystem results from dynamic interaction between different subsystems, most notably the nervous system, immune system, and endocrine system.

Following is a detailed but simple description of what we can learn about chronic pain from this systems perspective. And more importantly, what we can do about it.

First, a bit of warning. This article is a little bit on the long side. But it's one of the best articles I've written. And I've thrown in lots of pictures and very cool examples to illustrate the points. So grab a cup of coffee and get ready to learn some fascinating concepts that will give you insight into almost anything involving human health.

Complex adaptive systems defined

A system is a related set of parts that interact to serve a common objective.

A complex system is composed of parts that interact to produce collective behaviors that are more complex than the sum of the individual behaviors. For example, in economies, ecologies, weather, traffic flow, bird flocks, and schools of fish, the individual agents behave in a simple way, but their interactions produce an orderly pattern that is very complex.

A complex adaptive system, such as an organism, is one whose behavior is not merely reactive to its environment, but purposeful and proactive. Thus, a complex adaptive system has some degree of agency and intelligence.

Examples include beehives, insect colonies, and the immune system. In each case, the individual players in the system robotically obey patterns of behavior that are very simple. But the interactions produce a collective behavior that is highly intelligent and adaptive.

Where does this intelligence come from if not the individual players in the system?

Emergence and lack of central control

The behavior of a simple system is often governed by a central controller. For example, in a home heating system, the thermostat controls whether the heat turns on or off.

In a complex system, control is not located in any particular area, but emerges from the complex interactions of all the different parts. For example, a termite colony is an incredibly sophisticated architectural project, but there is not a single termite that knows how to build it. Instead, each termite is just following its own simple algorithm for behavior.

This reminds me of Dan Dennett's view on the nature of human intelligence: it cannot be localized in any one part of the brain. There is no "wonder tissue” imbued with magical powers of cognition, or homunculus that perceives sense data. Instead, cognition emerges from the complex interactions of billions of tiny cells, none of which are any smarter than a bacterium.

Similarly, the intelligence which coordinates the pain alarm system is not housed exclusively in the nervous system - it emerges from the nervous system’s interaction with other systems of the body, including the immune system and the endocrine system. Because the intelligence which creates pain is widely distributed throughout the brain and indeed the body, there is no central control switch that we can flip to get someone out of pain. Instead, we need to change the behavior of the system as a whole.

Nesting

Complex adaptive systems are nested - they are composed of subsystems, which are in turn composed of smaller subsystems, which have their own subsystems, etc. For example, the nervous system is made of parts like the brain, spinal cord and peripheral nerves, which are made of different types of cells, and so on.

Each subsystem has varying degrees of agency and intelligence. For example, a neuron can in some sense "decide" which neighbors to form synapses with. A termite can decide where to dig, etc.

We can turn our attention to various levels of hierarchy in the nested systems, zooming in and out of focus on different levels of complexity. There is nothing reductionistic or fallacious about considering the behavior of just one part of the whole, as long as we remember it is only a part.

For example, in examining why someone has pain, we can focus attention on the nociceptors. Although they are a relatively stupid and robotic little subsystem in the pain alarm supersystem, they do have some degree of intelligence, and can “decide" whether to report certain threats to the brain. We can alter their decision-making behavior, for example, by taking NSAIDS to reduce local inflammation and lower their sensitivity.

The dorsal horn of the spine is a more complex subsystem with more moving parts, and therefore more intelligence and agency. It receives nociceptive signals from the periphery and then decides whether to report them to the brain. Like the peripheral nerves, the sensitivity of the dorsal horn can be adjusted. For example, the brain can desensitize the dorsal horn through descending modulation.

As we look at higher level supersystems like the brain, we find far greater levels of intelligence and control over pain. Because this intelligence does not live in any particular place, but instead in a fabulously complex web of connections, creating change does not involve flicking any simple switches. Which might lead us to ask: why do complex systems change their behavior?

Homeostasis, stress and hormesis

Complex adaptive systems change so they can maintain a state of balance in relation to a changing environment.

Homeostasis is a state of balance providing the minimum or essential conditions for life. If the body does not preserve homeostasis by remaining within certain ranges of heat, fluid levels, blood pressure, it will die.

Allostasis refers to a slightly different concept – it is the dynamic process of changing states to adapt to the environment. Thus, an optimal state of balance is not static, but always shifting dynamically.

Stress is the process of using resources to respond to external or internal factors that push the system out of balance. For example, injury is a stressor that create a stress response. The stress response usually has three stages – alarm, resistance and recovery.

Hormesis occurs when a small amount of a certain stressor is beneficial, while larger amounts cause significant harm.

Exercise is the best known form of hormesis. The right dose - not too much not too little – helps tune and regulate the stress response system, making us healthier, and better able to withstand the same stressor in the future. What is less well appreciated is that the same rule applies to almost any kind of stressor, including exposure to toxins, heat, cold, anxiety, germs, etc. Thus, health is not necessarily served by reducing all forms of stress as low as possible. Instead, one should seek the optimum dosage of stress – not too high, not too low.

When the duration or intensity of stress is too high, the stress response may burn resources faster than they can be replenished. This can lead to a failure in recovery (exhaustion), and/or dysregulation of the stressed subsystem as discussed below.