Central sensitization is a condition of the nervous system that is associated with the development and maintenance of chronic pain. When central sensitization occurs, the nervous system goes through a process called wind-up and gets regulated in a persistent state of high reactivity. This persistent, or regulated, state of reactivity lowers the threshold for what causes pain and subsequently comes to maintain pain even after the initial injury might have healed.
Central sensitization has two main characteristics. Both involve a heightened sensitivity to pain and the sensation of touch. They are called allodynia and hyperalgesia. Allodynia occurs when a person experiences pain with things that are normally not painful. For example, chronic pain patients often experience pain even with things as simple as touch or massage. In such cases, nerves in the area that was touched sends signals through the nervous system to the brain. Because the nervous system is in a persistent state of heightened reactivity, the brain doesn't produce a mild sensation of touch as it should, given that the stimulus that initiated it was a simple touch or massage. Rather, the brain produces a sensation of pain and discomfort. Hyperalgesia occurs when a stimulus that is typically painful is perceived as more painful than it should. An example might be when a simple bump, which ordinarily might be mildly painful, sends the chronic pain patient through the roof with pain. Again, when the nervous system is in a persistent state of high reactivity, it produces pain that is amplified.
Chronic pain patients can sometimes think they must be going crazy because they know intellectually that touch or simple bumps shouldn’t be as uncomfortable or painful as they experience them. Other times, it’s not the patients themselves who think they are crazy, but their friends and loved ones. Friends and loved ones can witness the chronic pain patient grimacing at the slightest touch or crying out at the simplest bump and they think that the chronic pain patient must really be a hypochondriac or something. After all, the contrast between them and the chronic pain patient is stark: the friends and loved ones can be touched or get a bump and it doesn’t send them through the roof. The difference, though, is that the friends and loved ones don’t have a nervous system that is stuck in a persistent state of heightened reactivity, called central sensitization.
In addition to allodynia and hyperalgesia, central sensitization has some other characteristics, though they may occur less commonly. Central sensitization can lead to heightened sensitivities across all senses, not just the sense of touch. Chronic pain patients can sometimes report sensitivities to light, sounds and odors.1 As such, normal levels of light can seem too bright or the perfume aisle in the department store can produce a headache. Central sensitization is also associated with cognitive deficits, such as poor concentration and poor short-term memory.2 Central sensitization also corresponds with increased levels of emotional distress, particularly anxiety.3 After all, the nervous system is responsible for not only sensations, like pain, but also emotions. When the nervous system is stuck in a persistent state of reactivity, patients are going to be literally nervous – in other words, anxious. Lastly, central sensitization is also associated with sick role behaviors, such as resting and malaise,4 and pain behavior.5, 6
Central sensitization has long been recognized as a possible consequence of stroke and spinal cord injury. However, it has become increasingly clear that it plays a role in many different chronic pain disorders. It can occur with chronic low back pain,7, 8 chronic neck pain,9 whiplash injuries,10 chronic tension headaches,11, 12 migraine headaches,13 rheumatoid arthritis,14 osteoarthritis of the knee,15 endometriosis,16 injuries sustained in a motor vehicle accident,17 and after surgeries.18 Fibromyalgia,19 irritable bowel syndrome,20 and chronic fatigue syndrome,21 all seem to have the common denominator of central sensitization as well.
What causes central sensitization?
Central sensitization involves specific changes to the nervous system. Changes in the dorsal horn of the spinal cord and in the brain occur, particularly at the cellular level, such as at receptor sites.3, 22
As stated above, it has long been known that strokes and spinal cord injuries can cause central sensitization. It stands to reason. Strokes and spinal cord injuries cause damage to the central nervous system – the brain, in the case of strokes, and spinal cord, in the case of spinal cord injuries. These injuries alter the parts of the nervous system that are directly involved in central sensitization.
But what about the other, more common, types of chronic pain disorders, listed above, like headaches, chronic back pain, or limb pain? The injuries or conditions that lead to these types of chronic pain are not direct injuries to the brain or spinal cord. Rather, they involve injuries or conditions to the peripheral nervous system – that part of the nervous system that lies outside the spinal cord and brain. How do injuries and conditions associated with the peripheral nervous system lead to changes in the central nervous system, which, in turn, lead to chronic pain in the isolated area of the original injury? In short, how do isolated migraine headaches become chronic daily headaches? How does an acute low back lifting injury become chronic low back pain? How does an injury to a hand or foot become a complex regional pain syndrome?
There are likely multiple factors that lead to the development of central sensitization in these so-called ‘peripheral’ chronic pain disorders. These factors might be divided into two categories:
- Factors that are associated with the state of the central nervous system prior to onset of the original injury or pain condition
- Factors that are associated with the central nervous system following onset of the original injury or pain condition
The first group involves those factors that might predispose patients to developing central sensitization once an injury occurs and the second group involves antecedent factors that foster central sensitization once pain starts.
There are likely both biological, psychological, and environmental predisposing factors.
Low and high sensitivity to pain, or pain thresholds, are likely in part due to multiple genetic factors.1 While there is no research as of yet to support a causal link between pre-existing pain thresholds and subsequent development of central sensitization following an injury, it is largely assumed that one will be found.
Psychophysiological factors, such as the stress-response, are also apt to play a role in the development of central sensitization. Direct experimental evidence on animals23, 24 and humans,25, 26 as well as prospective studies on humans,27 have shown a relationship between stress and lowering of pain thresholds. Similarly, different types of pre-existing anxiety about pain is consistently related to higher pain sensitivities.28, 29 All these psychophysiological factors suggest that the pre-existing state of the nervous system is an important determinant of developing central sensitization following the onset of pain. It stands to reason. If the stress response has made the nervous system reactive prior to injury, then the nervous system might be more prone to become centrally sensitized once onset of pain occurs.
There is considerable indirect evidence for this hypothesis as well. A prior history of anxiety, physical and psychological trauma, and depression are significantly predictive of onset of chronic pain later in life.30, 31, 32, 33 The common denominator between chronic pain, anxiety, trauma, and depression is the nervous system. They are all conditions of the nervous system, particularly a persistently altered, or dysregulated, nervous system.
It's not that such pre-existing problems make people more prone to injury or the onset of illness -- as injury or illness is apt to occur on a somewhat random basis across the population. Rather, these pre-existing problems are apt to make people prone to the development of chronic pain once an injury or illness occurs. The already dysregulated nervous system, at the time of injury, for instance, may interfere with the normal trajectory of healing and thereby prevent pain from subsiding once tissue damage heals.
Factors leading to central sensitization following onset of pain
Antecedent factors can also play a role in the development of central sensitization. The onset of pain is often associated with subsequent development of conditions such as depression, fear-avoidance, anxiety and other stressors. The stress of these responses can, in turn, further exacerbate the reactivity of the nervous system, leading to central sensitization.3, 34
Poor sleep is also a common consequence of living with chronic pain. It is associated with increased sensitivity to pain as well.35, 36
In what’s technically called operant learning, interpersonal and environmental reinforcements have long been known to lead to pain behaviors, but it is also clear that such reinforcements can lead to the development of central sensitization.37, 38, 39
Treatments of central sensitization
Treatments for chronic pain syndromes that involve central sensitization typically target the central nervous system or the inflammation that corresponds with central sensitization. These are antidepressants,40 and anticonvulsant medications,41, 42, 43 and cognitive behavioral therapy.44, 45, 46 While usually not considered to target the central nervous system, regular mild aerobic exercise alters structures in the central nervous system47, 48 and leads to reductions in the pain of many conditions that are mediated by central sensitization. As such, mild aerobic exercise is used to treat chronic pain syndromes marked by central sensitization.49 Non-steroidal anti-inflammatories are used for the inflammation associated with central sensitization.3
Lastly, chronic pain rehabilitation programs are a traditional, interdisciplinary treatment that uses all of the above-noted treatment strategies in a coordinated fashion. They also take advantage of the research on the role of operant learning in central sensitization and have developed behavioral interventions to reduce the associated pain and suffering.50, 51 Such programs are typically considered the most effective treatment option for chronic pain syndromes.52, 53, 54, 55
For more information, please see these related topics: definition of pain, the neuromatrix of pain, the changing paradigms in chronic pain management, and the mission of the Institute for Chronic Pain to educate the public about empirical-based conceptualizations of pain and its treatments.
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Date of publication: March 23, 2013
Date of last modification: May 29, 2017