Central sensitization 1

No Brain, No PainHerkenning van centrale sensitisatie

in de manueel therapeutische praktijk

Mira Meeus, Kelly Ickmans, Margot De Kooning, Iris Coppieters, Jo Nijs

Central sensitization 2

PainProtection mechanismSubjective complex perceptionDifferent components, no consistent relation

→ Acute painCause / nociception

→ Chronic painSuffering and Behaviour

Central sensitization 3

Acute painPain receptors

Nociceptive neurons & Wide-Dynamic Range (WDR)

neurons in dorsal horn

Thalamus

Cortical regions

Cortical output

Central sensitization 4

Acute painMostly nociception:

◦A-delta fibres: fast◦C-fibres: slow,

high threshold

5Inwendige 2013-2014

Central sensitization 7

If pain still persistsIn chronic musculoskeletal disorders????

→ lack of distinct localisation→ lack of tissue damage

No longer adaptive function≠ prolonged acute pain

◦ Fibromyalgia, Chronic Fatigue Syndrome◦ Whiplash Associated Disorders ◦ Aspecific chronic low back pain

Central sensitization 8

Chronic painNociceptive mechanisms

CHRONIC PAIN

Non-nociceptive mechanisms

CNS: “Body still in danger” Nociceptive system changes

Peripheral and central hypersensitivity

probably not:no tissue damageno spatial localisation

Central sensitization

Chronic painWidespread, no distinct localisationNo source of nociceptionTherapy resistant, bad recovery

Central hypersensitivity or sensitization

9

Central sensitization 10

central sensitization

normal situation

Central sensitization

Central sensitization

= Hyperexcitability CNS = Hypersensitivity for all mechanic stimuli

AllodyniaGeneralized hyperalgesia

Referred painChronic pain

12

Central sensitization 13

Symptoms of central sensitizationNijs et al. Manual Therapy 2010;15:135-141.

Central sensitization

Central Sensitization

Neuroplasticity: Habituation & sensitization

prolonged or strong stimulation

= Functional & chemical changes:

- More receptors- Ion channels longer open- Expansion involved regions- …

Efficacy signal trandsduction ↗↗14

Central sensitization 15

Central Sensitization: plasticity

Central sensitization 16

Central Sensitization: mechanisms

1. Overactivation bottom-up system:↗ nociceptive transmission

Meeus & Nijs, 2007Nijs & Van Houdenhove 2008Yarnitsky et al. 2010

Central sensitization 17

Overactive bottom-up

Central sensitization

CS: Wind-up

18

C-fibres:- prolonged discharge- ubiquitous distribution- 1/3” temporal summation

Central sensitization 19

Central sensitization 20

central sensitization:

Wind-up ↗

normal situation

21Inwendige 2013-2014

22Central sensitization

CS: Wind-up → LTP

2.

3.

1.

4.

5.

LTPCS

Once CS, not necessarily dependent anymore of

nociceptive activity.

Central sensitization 23

Central SensitizationHyperexcitability of dorsal horn (DH) neurons:

↑ spontaneous activity↑ receptive fields↑ stimulus responses↑ sensitivity for all mechanic stimuli

AllodyniaHyperalgesia

Widespread pain

Central sensitization 24

Wind-up & Central Sensitization?

Also in No sourceHealthy of nociception?individuals?

Central sensitization 25

Central Sensitization: plasticity

Central sensitization 26

Central Sensitisation: mechanisms

Meeus & Nijs, 2007Nijs & Van Houdenhove 2008Yarnitsky et al. 2010

Changes in top-down pathways:

Inhibitory

Facilitatory

Central sensitization

CS: Impaired pain inhibition

Descending inhibitory pathways in dorsolateral funiculus:

◦Inhibitory substances (serotonin, opioids, etc.) in synapses in dorsal horn

Experimental block or lesions of pathways

→ equivalent of CS

27

Central sensitization

CS: Impaired pain inhibitionSpinal block inhibition

expansion receptive fields hypersensitivity faster Wind-up

Þ Presynaptic activity not essential for CSÞ CS by failing endogenous pain inhibition

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central sensitization

normal situation

Central sensitization 30

CS: Impaired pain inhibition

Conditioned pain modulation

Daenen et al. 2013: effect CPM on TS in WAD

Central sensitization 32

Conditioned pain modulation

Diffuse noxious inhibitory control or CPM:

◦CFS (Meeus et al 2008): ↘◦WAD (Daenen et al 2013): ↘◦FM (Julien et al. 2005, Staud et al. 2003, …) ↘◦RA (Leffler et al. 2002) =◦ …

Central sensitization 33

CS: Impaired pain inhibition

Exercise induced analgesia

8

20 x

6

Chronic WAD

PPTForce [N]

Van Oosterwijck et al. 2012

EIA 3/12/13 36

Descheemaeker et al. In Progress

Fibromyalgia

Lannersten and Kosek 2010

Shoulder myalgia & Fibromyalgia

EIA 3/12/13 37

38

Fibromyalgia (Lannersten & Kosek, 2010).

Central sensitization 39

Central Sensitization: plasticity

Central sensitization 40

Central Sensitisation: mechanisms

Meeus & Nijs, 2007Nijs & Van Houdenhove 2008Yarnitsky et al. 2010

Changes in top-down pathways:

Inhibitory

Facilitatory

Central sensitization 41

catastrophizing

kinesiophobia

somatization

stress

depression

CS: Cognitive eomotional sensitization

Zusman, 2002

Central sensitization 42

Psychosocial factorsYellow flagsPoor prognosisRelated to brain changes

Lloyd et al. 2008, George et al. 2007, Flor et al. 2002, Gracchev et al. 2002,2003

Catastropizing

Catastrophizing ≈ increased activity in brain areas related to:

◦ anticipation of pain, ◦ attention to pain (ACC), ◦ emotional aspects of pain ◦ and motor control. (Gracely, 2003)

Central sensitization 43

Central sensitization 44

pain

Overactive pain neuromatrix

Moseley, 2003

Catastropizing

- Prediction pain intensity in CFS: ± 20% (Meeus et al. 2012)

- Related to CPM (Weissman-fogel et al. 2008)

- Related to TS (Goodin et al. 2013)

CATASTROPHIZING PREDICTS ENDOGENOUS PAIN MODULATION

Central sensitization 45

Central sensitization 46

Nociceptive pain

Neuropathic pain

Central sensitization

Neuropathic pain

Central sensitization

Neuropathic painHaanpää et al. Pain 2011

Non-neuropathic central sensitization pain

evidence abnormality / damage nervous system

≠ evidence abnormality / damage nervous system

medical cause ≠ medical cause

neuroanatomically logical neuroanatomically illogical

burning, shooting, or pricking ≠ burning, shooting, or pricking

sensory dysfunction is neuroanatomically logical

↑sensitivity at segmentally unrelated sites

Nociceptive pain

Central sensitization

Musculoskeletal pain

Disproportionate pain experience?

no Central Sensitization

Diffuse pain distribution?

Central Sensitization Inventory ≥ 40 ?Central Sensitization

YES

YES

YES

NO

NO

NO

no Central Sensitization

Central Sensitization

Criterion1: Disproportionate pain?

Severity of pain and related disability disproportionate to the nature and extent of injury or pathology

Examples:◦ chronic neck pain, no structural lesions on cervical scans,

segmentally unrelated pain areas and severe disability◦ knee osteoarthritis, too early for surgery, widespread

pain & severe disability

Criterion 2: Diffuse pain distribution?

One of the following options:Widespread painLarge pain area with a non-segmental

distribution Pain varying in (anatomical) locationBilateral pain / mirror pain (i.e. symmetrical pain

pattern)Hemilateral pain

Criterion 3: Hypersensitivity of non-musculoskeletal senses?

◦Smell ◦Light◦Sound ◦Touch ◦Drugs ◦Cold / heat

Central Sensitization InventoryMeasuring hypersensitivity to various stimuli:

◦ Certain smells, such as parfums, make me feel dizzy and sick◦ When I go to bed, my legs feel uncomfortable and restless◦ Stress enhances my physical symptoms◦ I am sensitive to bright light

Part A onlyCutoff = 40

Mayer et al. Pain Practice 2012; Neblett et al. Journal of Pain 2013

Musculoskeletal pain

Disproportionate pain experience?

no Central Sensitization

Diffuse pain distribution?

Central Sensitization Inventory ≥ 40 ?Central Sensitization

YES

YES

YES

NO

NO

NO

no Central Sensitization

Central Sensitization

Additional signs and symptoms

Abnormal therapeutic response Abnormal pain timeline Sleeping difficulties Memory- and concentration difficulties Fatigue Muscle weakness Phantom swelling Impaired tactile localization Dyskinaesthesia

catastrophizing

kinesiophobia

somatization

stress

depression

Cognitive emotional sensitization

Characteristic for chronic pain in general rather than central sensitization pain? How quantifying?

Central sensitization 59

Assessing central pain processing

Central sensitization 60

Assessing central pain processingExercise induced analgesia

Central sensitization 61

Assessing central pain processingConditioned Pain Modulation

PPT voor PPT na0

1

2

3

4

5

6

7

8

9

CONFM

Treatment responseCS possibly NOT at treatment initiation BUT during rehabilitation

◦ Post-exertional malaise

◦ Pain increase following hands-on treatment

◦ Poor treatment progress

◦ Symptoms expand to non-segmental related areas

Mira.Meeus@ugent.be

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