What is depression?

From time to time, most people feel down, blue, unhappy, or irritable. These kinds of depressed moods come and go in response to the normal problems of life.

Sometimes, however, depressed moods stay for weeks or months on end. They come to color a person’s view of life in general. Depressed people are down, irritable, unhappy and, on top of it all, they also feel powerless to change their mood and life’s circumstances. So, they also come to feel hopeless.

If these moods continue for an extended period of time, it’s called depression: down and upset, but also feeling powerless to do anything about it, and so therefore hopeless.

Depression is considered a mood disorder. Symptoms of depression are the following:

  • Down and upset mood most every day for more than two weeks
  • Reduced ability to tolerate normal life stressors and so becoming irritable or frustrated easily, impatient, or tearful easily
  • Little interest in engaging in pleasurable activities (e.g., turning down an invitation to a party and staying home instead)
  • Little motivation to engage in daily activities
  • Significant weight loss or gain, often respectively accompanied by decreased or increased appetite
  • Persistent difficulty sleeping or sleeping too much
  • Fatigue or loss of energy
  • Feeling worthless or lowered self-esteem
  • Recurrent self-criticism
  • Poor concentration and short-term memory
  • Persistent thoughts of death or outright thoughts/actions of killing oneself

To be depressed, people don’t have to have every symptom listed above. People tend to have more or less of these symptoms. Moreover, the symptoms they have tend to be more or less intense and impairing.

As such, healthcare providers diagnose depression when patients have at least a certain number and combination of these symptoms.

What causes depression?

The cause of depression is not fully known. It’s common in popular culture to believe that depression is the result of a chemical imbalance in the brain.

Experts in depression, however, acknowledge that this view is not fully correct. There is much more to the picture of what causes depression.

Researchers agree that depression is likely the result of two general factors:

  • Biological or genetic predisposition
  • Persistent stress

It’s well-known that stress changes the nervous system. These changes have physical and psychological consequences. Stress changes the nervous system in ways that lead to altered levels of brain and nervous system chemicals.1, 2, 3 These chemicals are called neurotransmitters and stress hormones. Some of the stress hormones double as neurotransmitters. In turn, these chemicals affect mood, thinking, and behavior, as well as other bodily systems like the gastrointestinal, cardiovascular, and immune systems.

In certain people, such as those who are predisposed to depression, these stress-related changes affect the nervous system in ways that lead to depressive changes in mood, thinking, and behavior.4 In other people, who might be biologically predisposed to other types of conditions, stress-related changes to the nervous system lead to other types of problems in mood, thinking and behavior, or they might lead to problems in the other bodily systems.

As such, most experts agree that for depression to occur both stress-related changes to the nervous system and a predisposition for the nervous system to change in depressive ways are necessary.5 The combination of these factors produces alterations in brain chemicals – neurotransmitters and stress hormones – which leads to depressed mood, thinking and behaviors.

Link between depression and chronic pain

Depression is common among people with chronic pain.6 The majority of depressive episodes occur following onset of chronic pain.7 Numerous investigators have suggested that there must be a common pathway from chronic pain to depression. The likely pathway is the nervous system and its response to stress.

Chronic pain is, of course, a health condition. Health conditions such as back injuries, migraines or arthritis can cause chronic pain. Nonetheless, while it is a health condition, it is also a chronic stressor. It’s physically and emotionally stressful to live in pain all the time. The stress associated with chronic pain affects the nervous system like any other form of stress. In persons already predisposed to depression, the chronic pain leads to chronic stress, which, in turn, changes the nervous system in ways that bring about depression.

Depression makes chronic pain worse

Once depressed, depression can exacerbate chronic pain. It is explainable in terms of both psychological processes and physiological processes.

Psychologically, depression lowers what’s called a person’s frustration tolerance. Frustration tolerance is the ability to handle or deal with problems without getting upset. As people get depressed, their threshold for dealing with problems gets less and less. The things that they used to be able to handle well start to bug them or make them upset. As such, when depressed, people become irritable more easily. They get frustrated or impatient more easily. They become tearful more easily. In general, this aspect of depression is called lowered frustration tolerance.

Depression similarly lowers the ability to deal with chronic pain. As a person with chronic pain gets depressed, pain becomes harder to tolerate, even if, theoretically, the pain level remained the same. Why? It's because the depressed person's tolerance level gets lowered. Once depressed, you just can’t deal with it like you used to. As such, the experience of pain becomes more intense.

In this way, the onset of depression can start a vicious cycle of chronic pain and depression, both of which make each other worse. The more depressed people with chronic pain get, the more pain they experience, which then leads to a greater sense of powerlessness and hopelessness, which subsequently leads to greater depression and more pain.

painPhysiologically, this vicious cycle is explainable through the development of central sensitization. Central sensitization is a condition of the nervous system. The nervous system becomes stuck in a state of heightened reactivity. Central sensitization is what happens when chronic pain chronically stresses out the nervous system as described above. Pain thresholds lower because the nervous system changes and becomes highly reactive. As such, the threshold for stimuli to cause pain lowers.

People with chronic pain tend to exhibit a touch-me-not reaction in the area of their pain. Things that are normally not painful or not very painful – like touch or a mild bump – get registered by the brain as in fact very painful. People without chronic pain often react to people with chronic pain as if they must be hypochondriacs. The truth is, though, that chronic pain involves central sensitization, which makes the brain and the rest of the nervous system set in a ‘hair-trigger’ mode of reactivity.

Numerous investigators have found a link between chronic pain, central sensitization and depression.8, 9, 10, 11 The common pathway from chronic pain to depression is the nervous system becoming stuck in a persistent state of reactivity called central sensitization.

The vicious cycle described above is thus explicable in terms of chronic pain, central sensitization and depression.

Treating depression in chronic pain rehabilitation programs

Chronic pain rehabilitation programs are the only form of chronic pain management that makes it a point to also focus on treating depression. In such programs, patients acquire the abilities to self-manage pain, return to work, and overcome any secondary complications of living with chronic pain, like depression.

Chronic pain rehabilitation programs routinely utilize the most effective treatments for depression, such as cognitive behavioral therapy, antidepressant medications, and mild aerobic exercise.

It is possible to learn to live well despite having chronic pain, and in the process overcome depression.


1. Dranovsky A. & Hen, R. (2006). Hippocampal neurogenesis: Regulation by stress and antidepressants. Biological Psychiatry, 59, 1136-1143.

2. Malberg, J. E. (2004). Implications of adult hippocampal neurogenesis in antidepressant action. Journal of Psychiatry and Neurosciences, 29, 196-205.

3. Tanaka, M., Yoshida, M., Emoto, H., & Ishii, H. (2000). Noradrenaline systems in the hypothalamus, amygdala, and locus coeruleus are involved in the provocation of anxiety: Basic studies. European Journal of Pharmacology, 405, 397-406.

4. Heim, C., Newport, D. J., Mietzko, T., Miler, A. H., & Nemeroff, C. B. (2008). The link between childhood trauma and depression: Insights from HPA axis studies in humans. Psychoneuroendocrinology, 33, 693-710.

5. Banks, S. M., & Kearns, R. D. (1996). Explaining high rates of depression in chronic pain: A diathesis-stress framework. Psychological Bulletin, 119, 95-110.

6. Breivik, H. Collett, B., Ventafridda, V., Cohen, R., & Gallacher, D. (2006). Survey of chronic pain in Europe: Prevalence, impact on daily life, and treatment. European Journal of Pain, 10, 287-333.

7. Knaster, P., Karlsson, H., Estlander, E. M., & Kalso, E. (2012). Psychiatric disorders as assessed with SCID in chronic pain patients: The anxiety disorders precede the onset of pain. General Hospital Psychiatry, 34, 46-52.

8. Klauenberg, S., Maier, C., Assion, H., et al. (2008). Depression and changed pain perception: Hints for a central disinhibition mechanism. Pain, 140, 332-343.

9. Pollard, L. C., Ibrahim, F., Choy, E. H., & Scott, D. L. (2012). Pain thresholds in rheumatoid arthritis: The effect of tender point counts and disease duration. Journal of Rheumatology, 39, 28-31.

10. Tietjen, G. E., Brandes, J. L., Peterlin, B. L., et al. (2009). Allodynia in migraine: Association with comorbid pain conditions. Headache, 49, 1333-1344.

11. Maletic, V. & Raison, C. L. (2009). Neurobiology of depression, fibromyalgia, and neuropathic pain. Frontiers in Bioscience, 14, 5291-5338.

Date of publication: March 25, 2014

Date of last modification: September 8, 2016

Murray J. McAllister, PsyD, is a pain psychologist and consults to health systems on improving pain. He is the editor and founder of the Institute for Chronic Pain (ICP). The ICP is an educational and public policy think tank. In its mission is to lead the field in making pain management more empirically supported, the ICP provides academic quality information on chronic pain that is approachable to patients and their families. 

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