Understanding Central Sensitization:
Treating Central Sensitization:
Hyperalgesia is an increased response to a stimulus which is normally painful.
Allodynia is a term that describes the experience of pain arising from a stimulus which does not normally provoke pain.
Hyperalgesia has been frequently reserved for ‘nociceptor-mediated’ stimulus-evoked pain, whereas allodynia was regarded to be stimulus-evoked pain, mediated by receptors other than nociceptors. The usefulness of the concept allodynia in contrast to hyperalgesia has been debated since its existence.
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Central Sensitization (CS)
Central Sensitization (CS) is a process that is yet to be fully understood but is thought to accompany many chronic pain syndromes, contributing to increased pain and suffering. CS is believe to be a potential complicating factor in chronic headaches, back pain, neck pain, fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders, interstitial cystitis, irritable bowel syndrome (IBS) and postsurgical pain. The list goes on.
In the quote above by Evel Knievel, it appears that his likely history of chronic pain related to his many injuries has led to this perfect description of hyperalgesia.
Understanding Central Sensitization
Understanding Central Sensitization and learning to recognize it’s manifestations is the first step in learning how to reduce it’s impact on quality of life.
Central sensitization represents an enhancement in the function of neurons and pain pathways caused by increases in nerve excitability as well as reduced inhibition from higher levels in the brain. It is a manifestation of the remarkable plasticity (ability to change and adapt) of the nervous system in response to activity, inflammation, and nerve injury. The overall effect of central sensitization is to generate an increased or amplification of pain perception. Central sensitization is responsible for many of the changes in pain sensitivity in chronic pain. Because central sensitization results from changes in the properties of neurons in the central nervous system, the pain is no longer coupled to the presence, intensity, or duration of the original stimulus of pain. Instead, central sensitization produces pain hypersensitivity by changing the sensory response elicited by normal inputs, including those that usually evoke innocuous sensations.
See: YouTube explanation of Peripheral and Central Sensitization
The Evolution of Central Sensitization
Central sensitization is associated with the development and maintenance of chronic pain. It occurs when the nervous system goes through a process called “wind-up,” which is when repetitve stimulation of peripheral pain receptors (nociceptors) leads to ongoing repetitive impulses into the central nervous system. especially the dorsal horn neurons in the spinal cord, which leads to a persistent state of high reactivity or hypersensitivity. In other words, even after the original stimulus is gone, the nerves keeps signalling the central nervous system in the brain. As a result, sensory experience becomes amplified in the sense that a pain patient becomes hypersensitive to sensory stimulation most commonly including mechanical stimulation such as touch or pressure.
As a consequence, stimuli that previously would have been perceived as slightly painful now become moderately painful (hyperalgesia). Or being touched lightly or gently squeezed or hugged, normally not painful at all become painful (allodynia). These experiences are the hallmark of peripheral and central sensitivity. And such hypersensitivity is not limited to mechanical sensory stimuli but may extend into the other senses resulting in increased sensitivity or intolerance of heat or cold, light or sound and even smell. People may even develop emotional sensitivity becoming more impacted by anxiety and stress. One can begin to see the impact that CS can have on quality of life.
At least two pathways are proposed for central sensitization. The first is chronic processing of pain which causes changes in the nerves and peripheral nerve pathways which progress to central sensitization and the resulting clinical pain. The second, more psychologically centered pathway, is proposed as an alternative to the transformation of pain. This alternate pathway begins with elevated levels of chronic stress, and includes elements of anxiety, sleep disruption, decreased pain thresholds, and dysautonomia (dysfunction of the autonomic nervous system, see References below). It is common to find both proposed pathways actively involved in central sensitization syndrome. Central sensitization syndromes can be thought of as archetypal examples of a chronic biopsychosocial pain disorder.
Neurobiology of Central Sensitization
For those interested in the neurobiology of CS, this hypersensitive response to stimuli is thought to occur as a result of the over-bombardment of pain signals to the central nervous system which induces a number of pathophysiologic changes including neuro-immune dysfunction, neuro-endocrine dysfunction, NMDA dysregulation (NMDA a receptor involved in pain pathways – see Education – Pain), sympatho-afferent coupling; and altered serotonin and norepinephrine production and utilization. These events are thought to occur predominantly in the mid-brain and associated structures and are influenced by elements of the neuromatrix (the overall collection of nerves and neural pathways that make up the experience of pain including the psychological response to the experience). These pathophysiologic changes are associated with decreased descending inhibition, dysautonomia, and altered serotonin production/utilzation. The resulting depression, anxiety, sleep fragmentation, allodynia, and hyperalgesia characterize a number of chronic pain disorders.
Treating Central Sensitivity
Understanding these concepts and the two pathways proposed for the evolution of CS allows for the two basic approaches to limiting the development of CS and reducing it’s impact on one’s experience.
Treating the Central Sensitization Pain
While central sensitization is associated with all types of pain including inflammatory pain, the medications that appear to be most useful belong to the anti-epileptic class of drugs including gabapentin (Neurontin), pregabalin (Lyrica) and topiramate (Topamax) which act on nerves and the SNRI anti-depressants including duloxetine (Cymbalta), venlafaxine (Effexor) and milnacaprin (Savella) which act on the descending inhibitory nerve pathways from the brain.
NMDA Receptor Antagonists
Medications that block the NMDA receptors involved in pain pathways (see Education – Pain) are also believed to reduce or suppress CS. Medications that block NMDA receptors include ketamine, commonly used topically though current research is looking at use of intravenous ketamine. Methadone is thought to possibly provide some NMDA blocking activity which may contribute to it’s effectiveness in treating CS pain. Levorphanol, an older opioid recently re-introduced offers signiificant NMDA blocking activity and is likely the most effective opioid for the treatment of CS pain.
There is also recent research that suggest buprenorphine (Suboxone, Zubsolv, Bunivail) also has NMDA blocking activity that contributes to it’s effectiveness in treating chronic CS pain ( see Buprenorphine). Additionally, both levorphanol and buprenorphine are thought to have activity on the descending inhibitory pathways from the brain to the spinal cord as contributing mechanisms of their effectiveness for CS.
Medications with NMDA Antagonism, Possibly Effective for Central Sensitization:
- Dextromethorphan (Delsym)
- Orphenadrine (Norflex)
- Buprenorphine (Suboxone, Zubsolv, Bunivail)
Treating the CS Process
Underscoring the role of stress, anxiety and sleep deprivation in the evolution of central sensitivity, behavioral approaches to CS have been shown to be effective. Foremost along these lines are mindful exercises including meditation, deep relaxation techniques, yoga, tai chi, music therapy and hypnosis. Cognitive Behavior Training (CBT) has also been shown to be effective. Amongst the mechanisms proposed to explain how these behavioral approaches impact CS include the enhancement of the descending inhibitory pathways from the brain to the spinal cord similar to the mechanisms of the SNRIs, levorphanol and buprenorphine.
Recent research into the role of glial cells (non-neuronal cells that maintain and provide support and protection for neurons in the central and peripheral nervous system) suggests they play a significant role in central sensitization. As of yet, no effective treatment for CS that involve glial cells exists. There is very early, modest evidence however that palmitoylethanolamide (PEA), a natural supplement, may offer benefit in neuropathic and CS via its activity on glial cells. Unfortunately PEA is not readily available in the USA and can only be obtained from the Netherlands online.
Central Sensitization – Overviews
- How to explain central sensitization to patients with ‘unexplained’ chronic musculoskeletal pain – Practice guidelines – 2011
- The efficacy of pain neuroscience education on musculoskeletal pain A systematic review of the literature
- The clinical application of teaching people about pain – 2016
- Central Sensitization – A Generator of Pain Hypersensitivity by Central Neural Plasticity
- Central sensitization – Implications for the diagnosis and treatment of pain
- The Discriminative Validity of “Nociceptive,” ” Peripheral Neuropathic,” and “Central Sensitization” as Mechanisms-based Classifications of Musculoskeletal Pain – 2011
Central Sensitization – Back and Neck Pain
- Evidence for central sensitization in chronic whiplash – A systematic literature review
- Central Sensitization in Low Back Pain – Mechanisms-based classifications of musculoskeletal pain – Part 1 of 3 – Symptoms and signs of central sensitisation in patients with low back (+:- leg) pain – 2012
Central Sensitization – Fibromyalgia
see also: Fibromyalgia
- Fibromyalgia – The Unifying Concept of Central Sensitivity Syndromes
- From acute musculoskeletal pain to chronic widespre… [Man Ther. 2009] – PubMed – NCBI
- Fibromyalgia patients show an abnormal dopamine response to pain. – PubMed – NCBI
- Neurophysiologic evidence for a central sensitization in patients with fibromyalgia – 2003
- Fibromyalgia Syndrome- A Central Role for the Hippocampus—A Theoretical Construct
- What Fibromyalgia Teaches Us About Chronic Pain – 2013
- Evidence of central inflammation in fibromyalgia — Increased cerebrospinal fluid interleukin-8 levels 2012
- Central sensitization – a biopsychosocial explanation for chronic widespread pain in patients with fibromyalgia and chronic fatigue syndrome
- Current concepts in the treatment of fibromyalgia – 2013
- Innovative Approaches for the Complexity of Fibromyalgia – 2013
Central Sensitization – Headaches
- Central sensitization in photophobic and non-photophobic migraineurs
- Central sensitization in tension-type headache–possible pathophysi… – PubMed – NCBI
Central Sensitization – Musculoskeletal Pain
- Chronic whiplash and central sensitization; an evaluation of the role of a myofascial trigger points in pain modulation
- Peripheral and central sensitization in m… [Curr Rheumatol Rep. 2002] – PubMed – NCBI
- Myofascial Trigger Points – Peripheral or Central?
Central Sensitization (CS) Treatment
CS Treatment – CBT and Mindful Exercises
CS Treatment – Buprenophine
CS Treatment – Levorphanol
CS Treatment – Melatonin
CS Treatment – Methadone
CS Treatment – PEA
CS Treatment – Vitamin D
Emphasis on Education
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