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Central sensitisation: another label or

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useful diagnosis?
Jo Nijs,1,2 Andrea Polli,1,3 Ward Willaert,1,4 Anneleen Malfliet,1,2,3,4 Eva Huysmans,1,2,3,5 Iris Coppieters1,2,4
1
Pain in Motion International Research Group, Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education
and Physiotherapy, Vrije Universiteit Brussel, Belgium
2
Chronic pain rehabilitation, Department of Physical Medicine and Physiotherapy, University Hospital Brussels, Belgium
3
Research Foundation – Flanders (FWO), Brussels, Belgium
4
Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Sciences, Ghent University, Belgium
5
Department of Public Health (GEWE), Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium
Correspondence to Jo Nijs; Jo.Nijs@vub.be

Key learning points

 Chronic pain is a significant problem not only in the number of people affected but also in terms of health-related costs.
 Central sensitisation, a proposed physiological phenomenon is characterised by widespread hypersensitivity resulting from an
augmented response of central neurons to receptor activity, is present in many patients with chronic pain.
 Central sensitisation can be recognised by screening for disproportionate pain, assessing the distribution of pain through patient
pain drawing and using the Central Sensitisation Inventory questionnaire.
 If central sensitisation is present, it predicts poor outcome following classical local treatments such as electrotherapy, motor control
exercises and surgery.
 Treatment of patients in whom central sensitisation is present should address the (lifestyle) factors that sustain the process of
central sensitisation, including illness beliefs, stress, sleep, physical activity and diet.

Background pain sensations (insula, anterior cingulate cortex and prefrontal

Chronic pain affects up to 30% of the Western population with a cortex).11 The increased activity can also be found in brain-
prevalence higher than any other chronic disease.1 Chronic pain orchestrated nociceptive facilitatory pathways as well as in regions
is often of a non-specific nature, implying that there is no tissue not involved in acute pain sensations (various brain stem nuclei,
damage, or that tissue damage is not severe enough to explain dorsolateral frontal cortex and parietal associated cortex) and poor
the pain experience and/or related symptoms. This non-specific functioning of descending anti-nociceptive mechanisms.11–13 This
nature accounts for non-cancer pain as well as post-cancer pain activity seems to be fuelled by cognitive–emotional factors such as
(ie, pain in cancer survivors). Chronic pain has a significant personal catastrophic beliefs, stress, perceived injustice and anger.
and socioeconomic impact: among long-term conditions, it is
responsible for the highest number of years lived with disability and
is the most expensive cause of work-related disability.2–4 Chronic Which conditions are associated with CS?
pain also decreases life expectancy, in part due to excess deaths Potentially, every single person experiencing pain can develop CS,
from cancer and cardiovascular disease.5–7 but only a minority will. CS is a well-established feature in many
Over the past decades, neuroscience has advanced our people with chronic pain including those with chronic traumatic
understanding about pain, including the role of CNS sensitisation— neck pain (ie, whiplash), fibromyalgia, osteoarthritis, migraine,
more briefly termed central sensitisation (CS). The original irritable bowel syndrome, chronic fatigue syndrome and paediatric
definition for CS—‘an amplification of neural signaling within the pain.14–20 In other chronic pain conditions like low back pain, non-
CNS that elicits pain hypersensitivity’—originated from laboratory traumatic neck pain, tendinopathies, shoulder pain, rheumatoid
research, but nowadays the chronic pain management field has arthritis, pain following cancer and tennis elbow, CS is present in a
more or less accepted the need and importance of translating the minority (see table 1).21–27 Therefore, CS seems to be a continuum
concept of CS into clinic management.8,9 of altered nociceptive processing mechanisms in which greater
In many people with chronic non-specific pain, CS can explain symptoms of a certain condition are accompanied by more
why they suffer from pain in the absence of a clear origin of profound changes. For example, fibromyalgia will be located further
nociceptive input, or in the absence of enough tissue damage along the continuum than chronic low back pain.28
to explain the experienced pain severity, disability and other The usefulness of the label of CS can be questioned in certain
symptoms. CS encompasses various related dysfunctions within populations such as those with fibromyalgia where everyone seems
the CNS, all contributing to increased responsiveness to a variety to have it. However, understanding that CS helps explain the pain and
of stimuli-like mechanical pressure, chemical substances, light, other symptoms associated with fibromyalgia has clear treatment
sound, cold, heat, stress and electricity.10 Such CNS dysfunctions implications as discussed later. In addition, in those conditions where
include altered sensory processing in the brain with a disrupted CS is present in a minority of patients such as tendinopathies, the
resting state functional connectivity in the default mode network clinical importance of CS becomes clearer with studies showing that
and increased brain activity in areas known to be involved in acute CS is associated with higher pain severity and lower quality of life.27,29

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Table 1 Medical diagnoses associated with central translation.41,42 A Central Sensitisation Inventory cut-off score of 40 of
s­ ensitisation (CS) 100 has been recommended for screening purposes.41,43 In summary,
CS often present CS occasionally present one can expect the presence of CS in case of a disproportional pain
experience combined with a diffuse pain picture and/or a score above
Fibromyalgia Low back pain 40/100 on the Central Sensitisation Inventory. For more detailed
Chronic fatigue syndrome Shoulder pain information on the identification of CS in clinical practice, interested
Osteoarthritis Rheumatoid arthritis readers are referred to available resources regarding musculoskeletal
pain, post-cancer pain, osteoarthritis, chronic pelvic and perineal pain
Traumatic neck pain (whiplash) Idiopathic (non-traumatic) and low back pain.26,39,44–46
neck pain This clinical approach to recognising CS in clinical practice
Irritable bowel syndrome Tendinopathies does not tell us where or what central nervous dysfunctions are
Migraine Pain following cancer contributing to CS in the individual patient or what psychosocial
factor are involved. Hence, the label CS guides treatment
Tension type headache Tennis elbow
only in a very broad direction, not specifically targeting on the
Paediatric pain Patellofemoral pain syndrome dysfunction involved. More time-consuming options such as
Complex regional pain quantitative sensory testing are available to assess for instance
syndrome temporal summation, conditioned pain modulation and offset
analgesia.13,47,48
Neuropathic pain
Carpal tunnel syndrome How does a label of CS help in the management of pain?
Chronic pelvic and perineal Treatments that target local structures (ie, within the painful anatomical
pain region) are typically of little value in those with CS. This includes any
‘bottom-up’ approach, including surgical interventions, peripherally
Temporomandibular joint
acting drugs, hands-on interventions and dry needling. Hence, a more
disorder
‘central’ approach targeting brain and lifestyle interventions seem
warranted for treating CS.49 This may include centrally acting drugs
To put it another way, the subgroup of the population characterised such as antidepressants, but not opioids as their long-term use results
by CS will be more disabled and will suffer more from severe pain in opioid-induced hyperalgesia and consequently aggravation of the CS
than those who do not have CS. Also, CS predicts poor outcome in and problems associated with dependence.49,50
patients with tennis elbow, chronic pain following whiplash injury, Importantly, recognising CS in individual patients can be of
osteoarthritis, low back pain, whiplash and osteoarthritis.30–34 significant value to build a therapeutic alliance. Patients with
More specifically, the more CS, the poorer the response to local severe and spreading pain, as typically seen in CS, often ruminate
treatments (ie, treatments that target the presumed source of about their pain and the lack of help or understanding of the
nociception or try to decrease peripheral nociception). This includes problem. Explaining the concept of CS to patients by means of pain
physiotherapy, rehabilitation and also surgical interventions such as neuroscience education allows them to understand their condition,
subacromial decompression for shoulder impingement syndrome, to improve their pain/illness beliefs and coping strategies and
shoulder surgery in general, thoracic and/or lumbar fusion and consequently build the therapeutic alliance.51 The latter will
thoracotomy.33–38 Indeed, if patients have relatively high levels facilitate initiating more active lifestyle interventions, including
of CS preoperatively, the outcome 3 months after surgery will be a combination of stress management, sleep management,
significantly worse and patients may spend more time in hospital, dietary interventions, graded activity/graded exercise therapy
increasing healthcare costs substantially.35,37 Still, CS should not be and/or graded exposure depending on the patients’ individual
viewed as a medical diagnosis and should certainly not dismiss the characteristics.8,49,52
present diagnosis of, for example, low back pain, complex regional When treatment for chronic pain takes CS into account, it can
pain syndrome or even fibromyalgia. substantially improve symptoms and psychophysiological testing
reflecting CS alongside the clinical improvement (in terms of pain
How can we recognise CS? severity and functional improvement—medium to large effect
CS can be recognised clinically by a number of typical features, sizes).53 Cardinal to taking CS into account, is not relying on short-
including the spreading of pain and a combination of self-reported term changes in pain (severity). So short-term changes in pain
symptoms associated with CS (such as hypersensitivity to bright severity should not be relied upon when measuring the success
light, cold/heat, stress, odours). To recognise CS, patients should of therapy such as graded exercise. Understanding CS implies
have severe pain disproportionate to what one expect based on the that pain is no longer a reliable messenger. Moreover, adapting to
available tissue damage or presumed source of nociception.39 For variances in pain will reward the brain in producing pain. Hence,
example, patients having only mild knee osteoarthritis, yet suffering exercise therapy and physical activity using a time-contingent
from highly debilitating knee pain. Secondly, patients having CS often approach is warranted.
present with spreading pain, that is, pain that spreads outside the Taken together, treatment of patients having CS should not
segmental area of primary nociception. Applied to the example of focus on targeting local anatomical structures, but instead should
knee osteoarthritis, this criterion corresponds to someone having pain address the (lifestyle) factors that sustain the process of CS,
referring all over the affected low limb.40 Pain drawings (in which the including illness beliefs, stress, poor sleep, physical (in)activity and
patient marks areas affected by pain on an outline of a human body possibly even unhealthy diet by applying an individually tailored
with anterior, posterior and lateral views) can be used to standardise multimodal intervention.
and optimise the assessment of the individual’s pain distribution in
a reliable way. Finally, the combination and severity of symptoms
associated with CS can be easily assessed using part A of the Central Summary
Sensitisation Inventory, a 25-item questionnaire (scored 0–5; range Chronic pain has become a significant problem in the Western
0–100) generating reliable and valid data regardless of the language world, not only in relation to the number of people affected

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Information for patients

Do you often wonder why you continue to suffer from pain and no one seems to know how to help you? This is often due to the increased
sensitivity of your nervous system. If someone becomes injured, the nervous system turns on its alarm. This way one becomes aware
of the ‘danger’ and reacts appropriately by taking time to recover and find appropriate treatment. This is a system to protect the human
body and usually works very well. After a short period of time needed for the tissues to heal, the central nervous system returns into its
normal (resting) phase. Yet, in some patients, it stays erroneously in its alarm phase, even though the tissues have healed. This is what
may have happened in those who experience pain long after the tissues have healed. For some people, local treatments like massage,
muscle or joint treatments, infiltrations, surgery, locally acting drugs or electrotherapy provide little benefit. Instead, therapy should
target those factors that keep the central nervous system in the alarm phase and aim at calming down the nervous system. This may
involve a lifestyle approach including education, stress management, sleep management, physical activity management, exercise
therapy and/or dietary intervention.

but also in terms of health-related costs. Central sensitisation 10 Nijs J, Van Houdenhove B, Oostendorp RA. Recognition of central
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2010;15:135–41.
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present in many patients with chronic pain. It can be recognised patients and healthy controls. Eur J Pain 2008;12:1078–89.
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Cell Mol Life Sci 2009;66:375–90.
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