Central Sensitization
 

Central Sensitization

What is central sensitization?

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 subsequently comes to maintain pain even after the initial injury might be 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, the sensation of touch travels, of course, through the nervous system. Because the nervous system is in a persistent state of heightened reactivity, the sensation is registered in the brain as painful or uncomfortable even when it really shouldn’t, given that the sensation itself was that of a simple touch or massage. Hyperalgesia occurs when an actual painful stimulus 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, the sensation of pain travels through the nervous system, which is in a persistent state of high reactivity, and the pain is registered in the brain as a heightened level of pain.

 

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. Phillips, K. & Clauw, D. J. (2011). Central pain mechanisms in chronic pain states – maybe it is all in their head. Best Practice Research in Clinical Rheumatology, 25, 141-154. Central sensitization is associated with cognitive deficits, such as poor concentration and poor short-term memory. Yunus, M. B. (2007). The role of central sensitization in symptoms beyond muscle pain, and the evaluation of a patient with widespread pain. Best Practice Research in Clinical Rheumatology, 21, 481-497. Central sensitization also corresponds with increased levels of emotional distress, particularly anxiety. Curatolo, M., Arendt-Nielsen, L., & Petersen-Felix, S. (2006). Central hypersensitivity in chronic pain: Mechanisms and clinical implications. Physical Medicine and Rehabilitation Clinics of North America, 17, 287-302. 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, Wieseler-Frank, J., Maier, S. F., & Watkins, L. R. (2005). Immune-to-brain communication dynamically modulates pain: Physiological and pathological consequences. Brain, Behavior, & Immunity, 19, 104-111. and pain behavior. Meeus M., & Nijs, J. (2007). Central sensitization: A biopsychosocial explanation for chronic widespread pain in patients with fibromyalgia and chronic fatigue syndrome. Clinical Journal of Rheumatology, 26, 465-473. Melzack, R., Coderre, T. J., Kat, J., & Vaccarino, A. L. (2001). Central neuroplasticity and pathological pain. Annals of the New York Academy of Sciences, 933, 157-174.

 

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, Flor, H., Braun, C., Elbert, T., & Birbaumer, N. (1997). Extensive reorganization of primary somatosensory cortex in chronic back pain patients. Neuroscience Letters, 224, 5-8. O’Neill, S., Manniche, C., Graven-Nielsen, T., Arendt-Nielsen, L. (2007). Generalized deep-tissue hyperalgesia in patients with chronic low-back pain. European Journal of Pain, 11, 415-420. chronic neck pain, Chua, n. H., Van Suijlekom, H. A., Vissers, K. C., Arendt-Nielsen, L., & Wilder-Smith, O. H. (2011). Differences in sensory processing between chronic cervical zygapophysial joint pain patients with and without cervicogenic headache. Cephalalgia, 31, 953-963. , whiplash injuries, Banic, B, Petersen-Felix, S., Andersen O. K., Radanov, B. P., Villiger, P. M., Arendt-Nielsen, L., & Curatolo, M. (2004). Evidence for spinal cord hypersensitivity in chronic pain after whiplash injury and fibromyalgia. Pain, 107, 7-15. chronic tension headaches, Bendtsen, L. (2000). Central sensitization in tension-type headaches – possible pathophysiological mechanisms. Cephalalgia, 20, 486-508. migraine headaches, Stankewitz, A., & May, A. (2009). The phenomenon of changes in cortical excitability in migraine is not migraine-specific – A unifying thesis. Pain, 145, 14-17. rheumatoid arthritis, Meeus M., Vervisch, S., De Clerck, L. S., Moorkens, G., Hans, G., & Nijs, J. (2012). Central sensitization in patients with rheumatoid arthritis: A systematic literature review. Seminars in Arthritis & Rheumatism, 41, 556-567. osteoarthritis of the knee, Arendt-Nielsen, L., Nie, H., Laursen M. B., Laursen, B. S., Madeleine P., Simonson O. H., & Graven-Nielsen, T. (2010). Sensitization in patients with painful knee osteoarthritis. Pain, 149, 573-581. endometriosis, Bajaj, P., Bajaj, P., Madsen, H., & Arendt-Nielsen, L. (2003). Endometriosis is associated with central sensitization: A psychophysical controlled study. The Journal of Pain, 4, 372-380. injuries sustained in a motor vehicle accident, McLean, S., Clauw, D. J., Abelson, J. L., & Liberzon, I. (2005). The development of persistent pain and psychological morbidity after motor vehicle collision: Integrating the potential role of stress response systems into a biopsychosocial model. Psychosomatic Medicine, 67, 783-790. and after surgeries. Fernandez-Lao, Cantarero-Villanueva, I., Fernandez-de-Las-Penas, C, Del-Moral-Avila, R., Arendt-Nielsen, L., Arroyo-Morales, M. (2010). Myofascial trigger points in neck and shoulder muscles and widespread pressure pain hypersensitivity in patients with post-mastectomy pain: Evidence of peripheral and central sensitization. Clinical Journal of Pain, 26, 798-806. Fibromyalgia, Staud, R. (2006). Biology and therapy of fibromyalgia: Pain in fibromyalgia syndrome. Arthritis Research and Therapy, 8, 208. irritable bowel syndrome, Verne, V. N., & Price, D. D. (2002). Irritable bowel syndrome as a common precipitant of central sensitization. Current Rheumatology Reports, 4, 322-328. and chronic fatigue syndrome, Meeus M., & Nijs, J. (2007). Central sensitization: A biopsychosocial explanation for chronic widespread pain in patients with fibromyalgia and chronic fatigue syndrome. Clinical Journal of Rheumatology, 26, 465-473. 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 Schwartzman, R. J., Grothusen, R. J., Kiefer, T. R., & Rohr, P. (2001). Neuropathic central pain: Epidemiology, etiology, and treatment options. Archives of Neurology, 58, 1547-1550.

 

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 Central Sensitizationbrain, 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.

 

Predisposing factors

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 animals Alexander, J., DeVries, A., Kigerl, K., Dahlman, J., & Popovich, P. (2009). Stress exacerbates neuropathic pain via glucocorticoid and NMDA receptor activation. Brain, Behavior and Immunity, 23, 851-860. Imbe, H., Iwai-Liao, Y., & Senba, E. (2006). Stress-induced hyperalgesia: Animal models and putative mechanisms. Frontiers in Bioscience, 11, 2179-2192. and humans, Kuehl, L.  K., Michaux, G.  P., Richter, S., Schachinger, H., & Anton F. (2010). Increased basal mechanical sensitivity but decreased perceptual wind-up in a human model of relative hypocortisolism. Pain, 194, 539-546. Rivat, C., Becker, C., Blugeot, A., Zeau, B., Mauborgne, A., Pohl, M., & Benoliel, J. (2010). Chronic stress induces transient spinal neuroinflammation, triggering sensory hypersensitivity and long-lasting anxiety-induced hyperalgesia. Pain, 150, 358-368. as well as prospective studies on humans, Slade, G. D., Diatchenko, L., Bhalang, K., Sigurdsson, A., Fillingim, R. B., Belfer, I., Max, M. B., Goldman, D., & Maixner, W. (2007). Influence of psychological factors on risk of temporomandibular disorders. Journal of Dental Research, 86, 1120-1125. 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. Hirsh, A. T., George, S. Z., Bialosky, J. E., & Robinson, M. E. (2008). Fear of pain, pain catastrophizing, and acute pain perception: Relative prediction and timing of assessment. Journal of Pain, 9, 806-812. Sullivan, M. J. Thorn, B., Rodgers, W., & Ward, L. C. (2004). Path model of psychological antecedents to pain experience: Experimental and clinical findings. Clinical Journal of Pain, 20, 164-173. 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 is significantly predictive of onset of chronic pain later in life. Nahit, E. S., Hunt, I. M., Lunt, M., Dunn, G., Silman, A. J., & Macfarlane, G. J. (2003). Effects of psychosocial and individual psychological factors on the onset of musculoskeletal pain: Common and site-specific effects. Annals of Rheumatic Disease, 62, 755-760. Talbot, N. L., Chapman, B., Conwell, Y., McCollumn, K., Franus, N., Cotescu, S., & Duberstein, P. R. (2009). Childhood sexual abuse is associated with physical illness burden and functioning in psychiatric patients 50 years of age or older. Psychosomatic Medicine, 71, 417-422. McLean, S. A., Clauw, D. J., Abelson, J. L., & Liberzon, I. (2005). The development of persistent pain and psychological morbidity after motor vehicle collision: Integrating the potential role of stress response systems into a biopsychosocial model. Psychosomatic Medicine, 67, 783-790. 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.

 

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 Diatchenko, L., Nackley, A. G., Slade, G. D., Fillingim, R. B., & Maixner, W. (2006). Idiopathic pain disorders – Pathways of vulnerability. Pain, 123, 226-230.

 

Poor sleep is also a common consequence of living with chronic pain. It is associated with increased sensitivity to pain as well. Azevedo, E., Manzano, G. M., Silva, A., Martins, R., Andersen, M. L., & Tufik, S. (2011). The effects of total and REM sleep deprivation on laser-invoked potential threshold and pain perception. Pain, 152, 2052-2058. Chiu, Y. H., Silman, A. J., Macfarlane, G. J., Ray, D., Gupta, A., Dickens, C., Morris, R., & McBeth, J. (2005). Poor sleep and depression are independently associated with a reduced pain threshold: Results of a population based study. Pain, 115, 316-321.

 

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. Holzl, R., Kleinbohl, D. & Huse, E. (2005). Implicit operant learning of pain sensitization. Pain, 115, 12-20. Baumbauer, K. M., Young, E. E., & Joynes, R. L. (2009). Pain and learning in spinal system: Contradictory outcomes from common origins. Brain Research Reviews, 61, 124-143. Becker, S., Kleinbohl, D., Baus, D., & Holzl, R. (2011). Operant learning of perceptual sensitization and habituation is impaired in fibromyalgia patients with and without irritable bowel syndrome. Pain, 152, 1408-1417.

  

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 Hauser, W., Wolfe, F., Tolle, T., Uceyler, N. & Sommer, C. (2012). The role of antidepressants in the management of fibromyalgia: A systematic review and meta-analysis. CNS Drugs, 26, 297-307. and anticonvulsant medications, Hauser, W., Bernardy, K., Uceyler, N., & Sommer, C. (2009). Treatment of fibromyalgia syndrome with gabapentin and pregabalin – A meta-analysis of randomized controlled trials. Pain, 145, 169-181. Straube, S., Derry, S., Moore, R. A., & McQuay, H. J. (2010). Pregabalin in fibromyalgia: Meta-analysis of efficacy and safety from company clinical trial reports. Rheumatology, 49, 706-715. Tzellos, T. G., Toulis, K. A., Goulis, D. G., Papazisis, G., Zampellis, Z. A., Vakfari, A., & Kouvelas, D. (2010). Gabapentin and pregabalin in the treatment of fibromyalgia: A systematic review and meta-analysis. Journal of Clinical Pharmacy and Therapeutics, 35, 639-656. and cognitive behavioral therapy. Thieme, K. Flor, H., & Turk, D. C. (2006). Psychological pain treatment in fibromyalgia syndrome: Efficacy of operant behavioral and cognitive behavioral treatments. Arthritis Research & Therapy, 8, R121. Lackner, J. M., Mesmer, C., Morley, S., Dowzer, C., & Hamilton, S. (2004). Psychological treatments for irritable bowel syndrome: A systematic review and meta-analysis. Journal of Clinical and Consulting Psychology, 72, 1100-1113. While usually not considered to target the central nervous system, regular mild aerobic exercise alters structures in the central nervous system Erickson, K. I., Voss., M. W., Prakesh, R. S., et al. (2011). Exercise training increases size of hippocampus and improves memory. Proceedings of the National Academy of Sciences, 108, 3017-3022. Hilman, C. H., Erickson, K. I., & Kramer, A. F. (2008). Be smart, exercise your heart: Exercise effects on brain and cognition. Nature Reviews Neuroscience, 9, 58-65. 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. Busch, A. J., Barber, K. A., Overend, T. J., Peloso, P. M., & Schachter, C. L. (Updated August 17, 2007). Exercise for treating fibromyalgia. In Cochrane Database Reviews, 2007, (4). Retrieved May 16, 2011, from The Cochrane Library, Wiley Interscience. 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. Fordyce, W. E., Fowler, R. S., Lehmann, J. F., Delateur, B. J., Sand, P. L., & Trieschmann, R. B. (1973). Operant conditioning in the treatment of chronic pain. Archives of Physical Medicine and Rehabilitation, 54, 399-408. Gatzounis, R., Schrooten, M. G., Crombez, G., & Vlaeyen, J. W. (2012). Operant learning theory in pain and chronic pain rehabilitation. Current Pain and Headache Reports, 16, 117-126. Such programs are typically considered the most effective treatment option for chronic pain syndromes. Hauser, W., Bernardy, K., Arnold, B., Offenbacher, M., & Schiltenwolf, M. (2009). Efficacy of multicomponent treatment in fibromyalgia syndrome: A meta-analysis of randomized controlled clinical trials. Arthritis & Rheumatism, 61, 216-224. Flor, H., Fydrich, T. & Turk, D. C. (1992). Efficacy of multidisciplinary pain treatment centers: A meta-analytic review. Pain, 49, 221-230. Gatchel, R., J., & Okifuji, A. (2006). Evidence-based scientific data documenting the treatment and cost-effectiveness of comprehensive pain programs for chronic non-malignant pain. Journal of Pain, 7, 779-793. Turk, D. C. (2002). Clinical effectiveness and cost-effectiveness of treatments for patients with chronic pain. The Clinical Journal of Pain, 18, 355-365.

 

References

Last Updated on Sunday, 29 December 2013 14:33

Published on Friday, 27 April 2012 13:12

Written by Murray J. McAllister, PsyD

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