Stress, Inflammation and Chronic Pain

Nov 24, 2014

People with chronic pain know that they tend to have a pain flare when they are under stress. They are, however, sometimes sensitive to acknowledge it aloud for fear that others might think that their pain is all in the head. Nonetheless, the fact that stress makes pain worse is entirely normal and common. It is a natural product of how we are made.

In fact, stress has a much more significant role in the production of pain than simply making it worse. The development of pain itself, from acute injuries or illness to the long-term maintenance of chronic pain, incorporates what we call the stress response. In other words, were it not for our stress response, we would not have pain as we know it. To review the remarkable and significant role that the stress response has in pain, we would require much greater time and space than this blog post allows. [For a good review within the professional literature, please see Chapman, Tuckett, & Song (2008)].

Instead, in this post, let’s look at one way stress exacerbates pain and leads to what we typically call a ‘pain flare.’ We’ll focus our attention on a particular aspect of the stress response, which leads to increased pain: inflammation. Specifically, let’s review how stress triggers our normal and natural stress response, which subsequently produces inflammation that, in turn, makes pain worse.

The immune system

The immune system is our natural defense system. It works in conjunction with our nervous system and our endocrine (or hormone) system. Traditionally, we have always divided these systems up as if they are three separate systems, but we now know that they do not operate independently of each other. So, whenever we discuss the functioning of one system, as we are today discussing the immune system, we have to keep in mind that structures in the brain, the rest of the nervous system, neurotransmitters, and hormones are almost always also at play when the immune system functions as it does.

So what does the immune system do? Traditionally, we have understood the immune system to have a defensive role in response to injury or infection. When injury or infection occurs, the immune system produces inflammation. Inflammation is a catchall term used to describe a number of different types of chemical messengers and cells that fight off the infection or prepare for healing. For instance, it’s what makes us well when we are sick by fighting off viral or bacterial infections.

Many years of basic science in psychology and biology have allowed us to now know that inflammation also plays a role in changes in mood and behavior, both of which can also allow for fighting off infection or responding to injury with damage control (Sternberg, 2001). In more general terms, these psychological responses are also responses to danger. Indeed, we now think of the immune system, in conjunction with the nervous system and the endocrine system, as part of a three way response to danger, or what we call the stress response.

Stress response

The stress response is our natural cognitive, emotional, motivational, bodily, behavioral and social response to a danger, or what we might more generically call a ‘stressor.’ Take for example, thousands of years ago, we would have been likely living on the savannas of Africa and we would have faced various threats, such as the possibility of being attacked by lions.

In response to the stressor of a lion attack and its resultant injuries, we naturally and automatically react, without conscious awareness or intention, with our built-in stress response. A quick review of the multifaceted – or biopsychosocial – aspects of this stress response are the following:

  • Cognitive responses: Heightened focus on the danger, rapid learning about the danger and subsequent acute memory of the stressor, among others
  • Emotional responses: Heightened alarm, anger and/or fear, increased sense of social belonging, among others
  • Motivational response: Heightened drive to react, increased energy
  • Bodily responses: Among others, increased muscle tension, heart rate, blood pressure; increased glucose in bloodstream; increased immune response
  • Behavioral and social responses: fight-or-flight, and tend-and-befriend (i.e., some combination of taking on the danger or getting away from it and/or joining together, coming to the rescue, and protecting or caring for one another and wanting to be cared for) (Taylor, et al., 2000)

In later posts, we’ll discuss in more detail the various aspects of the stress response, but this quick overview is important for two reasons.

First, and foremost, we see clearly the larger context in which the immune system functions. Its defensive function is part of a greater whole and the whole is the protective, or defensive, function of the stress response. From here, we can also see how the stress response is a whole contingent of automatic responses, from the microscopic to the macroscopic, that occurs when we are threatened by danger. In other words, it is the stress that the human organism undergoes when threatened.

Second, we see that in our society we tend to categorize these microscopic to macroscopic responses under particular headings, such as those that are biological, those that are psychological, and those that are social. We subsequently tend to think that these categories represent actually different things and then begin to wonder how they are connected. However, these categories do not represent distinct kinds of things. They are heuristic categories that reflect different aspects of the same kind of thing, the human organism, or person. In this way, we no longer wonder how “the mind” is connected to “the body,” as if they are two separate kinds of things. No, the cognitive, emotional, motivational and social aspects of the stress response occur within the same kind of thing as the biological and behavioral aspects of the stress response do. That is to say, they occur within a person, not some separate entities called “a mind” or “a body.” As such, in science and healthcare, we typically no longer refer to this mental/physical or mind/body distinction, but rather refer to these aspects of a person with the term ‘biopsychosocial.’


So, the stress response involves many natural, automatic responses and one of them is the immune system kicking into high gear to produce inflammation (Kiecolt-Glaser, et al., 2002). This response clearly makes sense. If we go back to the example of a lion attack, we will have a greater chance of surviving if our immune system is functioning in high gear as it fights off any infections from the scratches or bites that we might get.

This peak performance is the product of the immune system working in conjunction with the sympathetic nervous system and the endocrine (or hormone) system. Specifically, different structures in the brain, associated with the fight-or-flight response, send messages via a highway of nerves to the pituitary and adrenal glands, which then produce hormones such as cortisol and adrenaline (also known as epinephrine). These are often called ‘stress hormones’ and they are responsible for getting us ramped up. For instance, cortisol prevents insulin (another hormone that’s produced in the pancreas) from working well and so glucose (i.e., sugar) increases in the bloodstream, giving us increased energy. Initially, these hormones also start the immune response in the form of white blood cells and what are called cytokines. We call this immune system response ‘inflammation.’

Inflammation is what occurs when, upon injury, the injured area becomes red, swollen, and sensitive to the touch. The redness and swelling is our immune system at work, the white blood cells and cytokines engaging in their protective function, engaged in damage control. The sensitivity comes because the immune response irritates the nerves in the area. At this stage, this irritation is good because it serves a protective function. If the injured area is sensitive to the touch, it is going to prevent us from using it or poking it too much or otherwise re-injuring it. Subsequently, we are motivated to protect or guard the area. We’ll come back to this point.

At this time, there are also cytokines in the brain too intermingling with its hormones and neurotransmitters. If the injury or infection is severe enough or widespread enough, this mix of chemicals in our nervous system, including the brain, further lead to a run down feeling, which we call ‘malaise.’ It’s the ‘blah’ feeling we have when sick: run down, achy, fatigued, and unmotivated to do anything but lay around and rest. We are also motivated at this stage to need others, associate with them, and depend on them for help. In other words, we feel upset, perhaps even a bit abandoned, when others ignore us when we are sick or injured. We’ll come back to this point too.

After some time, these processes unfold and the threat passes (for example, microscopically, the infection and injuries from the lion attack have been successfully warded off and subsequently healed, just as we might have banded together, at a macroscopic level, to fight off the actual attack in the first place). Subsequently, cortisol tells the brain to start turning off the stress response.

The whole process is remarkable, even amazing. At all the multifaceted levels, from the microscopic to the macroscopic, we are made to survive. The stress response is an almost beautiful, elegant way to optimize our chances of survival when threatened by danger.

We still respond to threats, or stress, with the stress response

Admittedly, lions don’t attack us much anymore. With some few exceptions (such as the occasional natural disaster or bad car accident, or the activities of soldiers and first responders), our life and limbs don’t get threatened very often in our present day and age. We still, however, face threats.

The threats that we most commonly face nowadays are psychological and social in nature. They are the death of a spouse or child or other family member or friend. They are the loss of a job and subsequent loss of income. They are the bankruptcies and home foreclosures. They are the overly critical bosses or the fights with a sister or brother or when best friends move away. They are a son or daughter joining the armed forces and going off to war. They are the occasions when a family member comes down with a serious illness, say, cancer. They are the times when we have to live with a chronic illness, such as chronic pain. These kinds of stressors are not threats to life or limb, on the order of a lion attack or combat, but nonetheless they are threats. They are threats to our livelihood and well-being.

As such, we are hard-wired to respond to such stressors with the stress response.

Moreover, we also have the ability to anticipate the above-noted psychological and social threats. That is to say, the kinds of threats listed above are not the only kinds of threats that we commonly face. We also face the threat of anticipating the potential for those kinds of stressors.

We call it anxiety. It is the worrying or ruminating or fretting about the possibility that we face any of those threats listed above – the loss of a job, the loss of an income, the home foreclosure, the overly critical boss, the well-being of our loved ones, the loss of our health, the living with pain and all the problems that occur as result.

Human beings have an amazing capacity to worry about everything that could go wrong. In a sense, it’s a form of the stress response, preparing us for danger. However, anxiety or worry is what happens when our stress response has become stuck in the ‘on’ position. When anxious, in other words, we continue to prepare for danger or threat even when there is no actual threat, just the possibility of one.

Either way – whether we are actually living through a stressor or worrying about the possibility of a stressor, we still automatically, and without much conscious intention, still respond to such threats with the stress response.

Stress and inflammation make pain worse

If you have a chronic pain condition, you know that stress makes it worse. From here, we can see why. When experiencing a stressful event like those listed above or when worrying about the possibility of such a stressful event, you automatically, and without conscious intention, react with the stress response. Your immune system, in conjunction with your nervous system and endocrine system, puts out inflammation in response to the real or perceived threat. This inflammation causes irritation to your nerves, including the nerves in the area of your chronic pain. As a result, the nerves become more sensitive, just as they are supposed to do when the immune system is engaged in the stress response. With the nerves more sensitive due to the increased inflammation, they subsequently require less stimuli to cause pain and you experience increased pain with your normal activities.

For instance, suppose that you have chronic low back pain and usually it doesn’t hurt to get out of a chair. However, when under stress, the stress response leads to higher levels of inflammation, which make the nerves in your low back more sensitive. As a result, the stimuli involved in the act of getting out of a chair makes your low back painful when ordinarily you can get out of a chair without pain at all. What you experience in such instances is the all-too-common exacerbation of pain due to stress.

Notice that your immune system is doing exactly what it is made to do when under threat. While problematic, it is normal and common.

It can become increasingly problematic when the stressor remains unresolved and subsequently goes on for some time. The threat is on-going and so the stress response continues unabated. The level of inflammation becomes higher and higher. The nervous system as a whole becomes more sensitized. As a result, widespread inflammation can lead to both increasing pain and more widespread pain, in the form of body aches.

Moreover, as we saw above, widespread inflammation can lead to malaise, an overall 'blah' feeling. You become fatigued and unmotivated to do anything but rest. In addition to higher levels of pain or possibly even more widespread pain, you are now not feeling well. You feel like you have the flu, but without the flu.

At the same time, your needs for others increase. It is the result of the tend-and-befriend aspect of the stress response. These needs are the needs for others to provide comfort and care. You don’t want to be left alone and, if you are, it’s like adding insult to injury.

Now, some people might not want to admit that such emotional and social needs arise when not feeling well. For after all, we have a sense from society that we are supposed to remain strong and independent. If we don’t, we have a good likelihood that we'll face stigma.

It’s important to recognize, however, that such emotional and social needs are built right into us when the stress response kicks in and, particularly, when it goes on for some time. It’s important to understand that you are not just being weak. The stress response is doing exactly what it is supposed to do in response to a threat against your well-being.

It’s okay to acknowledge it. It is a common and natural consequence to stressors, or threats.

What you can do about chronic pain

With that said, however, it’s also important that you recognize that you are not helpless to it.

Chronic pain rehabilitation programs are a traditional form of chronic pain management that focuses on reducing the stress response in the presence of pain. Through multiple therapeutic modalities, they focus on reducing the reactivity of the nervous system and teaching you how to maintain this reduced reactivity of the nervous system, which, in turn, leads to less inflammation and less pain, greater energy and motivation, and greater abilities to independently do what you want to do. The Institute for Chronic Pain has a number of resources that provide information on chronic pain rehabilitation.

A brief list follows:


Chapman, C. R., Tuckett, R. P., & Song, C. W. (2008). Pain and stress in a systems perspective: Reciprocal neural, endocrine and immune interactions. Journal of Pain, 9, 122-145.

Kiecolt-Glaser, J. K., McGuire, L., Robles, T. R., & Glaser, R. (2002). Emotions, morbidity, and mortality: New perspectives from psychoneuroimmunology. Annual Review of Psychology, 53, 83-107.

Sternberg, E. M. (2001). The balance within: Science connecting health and emotions. New York: W. W. Freeman.

Taylor, S. E., Klein, L. C., Lewis, B. P., Gruenewald, T. L., Gurung, R. A., & Updegraff, J. A. (2000). Biobehavioral response to females: Tend-and-befriend, not fight-or-flight. Psychological Bulletin, 107(3), 411-429.

Author: Murray J. McAllister, PsyD

Date of last modification: 5-10-2017

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