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Chronic pain in children:pathophysiology
Guy Hans
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Definition of chronic pain?
• “An unpleasant sensory and emotionalexperience associated with actual or potentialtissue damage, and lasts beyond the normal time for healing.”
• “Chronic pain in children is the result of adynamic integration of biological processes, psychological factors, and sociocultural context considered within a developmental trajectory.”
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• Chronic pain in children…
• … clinical reality or rather an exceptional condition?
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Physiology of acute pain
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The BIOMEDICAL Model
• Pain as a sensory event reflecting underlying disease or tissue damage
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Physiological method of protection↓
Body is warned against further tissue damage↓
React in a proper manner⇓
SURVIVAL
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Transmission of nociceptive signal
Jane W. Ball and Ruth C. BindlerChild Health Nursing: Partnering with Children & Families
© 2006 by Pearson Education, Inc.Upper Saddle River, New Jersey 07458
All rights reserved.
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Presence of pain complaints
damage ≠ to painpain ≠ to lesioning
Pain without lesion/tissue damage is possible:
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Kidd, Urban. Br J Anaesthesia 2001;87(1).
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Development of chronic pain
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Chronic Pain
Hyperalgesia Allodynia
The Role of Plasticity in Chronic Pain
Injury
Acute Pain
Healing With PlasticityNormal Healing
Pain Relief
Adapted from Marcus DM. Am Fam Physician. 2000;61:1331-1338.
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With Permission. Woolf,2000.
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Consequences of central sensitization
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Risk factors of central sensitization …
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Gate Control Theory
Melzack R. In: Cousins MJ, Bridenbaugh PO, eds. Neural Blockade in Clinical Anesthesia and Management of Pain. 3rd ed. Philadelphia, Penn: Lippincott Williams & Wilkins; 1998.
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Milan MJ, Progress in Neurobiology 66, 2002.
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Hyperalgesia Sensitization
pain threshold threshold for response
pain to suprathreshold response to stimuli suprathreshold stimuli
Spontaneous pain Spontaneous activity
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SENSITIZING ‘SOUP’Hydrogen Ions Histamine Purines
Noradrenaline Potassium Cytokines
Bradykinin Prostaglandins NGF
Leukotrienes 5-HT Neuropeptides
Tissue Damage
Woolf, Chong. Anesth. Analgesia (77), 1993.
Peripheral Sensitization
Inflammation Sympathetic Terminals
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SKIN
Peripheral Sensitization
PeripheralNerve
Terminal
Pressure ?
Plasma ExtravasationVasodilation
Heat 5-HT3 PGE2Bradykinin
VR1 5-HT3 EP B1/B2
IL1ß
MastCell
Macrophage
(PKC)
TNF-αIL-6LIF
IL1-R TrkAH+
PKCTTXr
(SNS/SNS2)
Sub P
Gene Regulation
TTXr
TTXs
H+
P2X ASIC
Adapted from Woolf CJ, et al. Science. 2000;288:1765-1768.
TissueDamage
ATPNGF
H1
Histamine
Ca2+
PKA
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With permission. Jensen TS et al. Acta Anaesth Scand, 45, 2001.
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Mechanisms of nociceptive central pain1. Autosensitization of receptors
2. Ectopic firing of DRG cells
3. Calcium-induced molecular cascades from excess glutamate
4. Phenotypic change of A-β cells and DRG
5. Changes in gene expression of sodium channels and neuropeptides
6. Anatomic changes at dorsal horn
Schwarzman et al. Neurological Review, 58, 2001.
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Neuropathic Pain Is Defined as…
…Pain caused by a lesion or dysfunction of the nervous system1
• Nerve sensitization or damage can be located in the peripheral or central nervous system1
• Manifests with sensory symptoms and signs2
• May have both positive and negative sensory and motor symptoms and signs2
1. Merskey H, Bogduk N, eds. Classification of Chronic Pain. 2nd ed. Seattle, WA: IASP Press; 1994.2. Backonja MM. Anesth Analg. 2003;97:785-790.
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Examples of Peripheral vs. Central Sensitization
Adapted from Woolf CJ, Mannion RJ. Lancet. 1999;353:1959-1964.
Sensory function after nerve injury with spontaneous firing along axon
No Stimulus Pain
SensationNociceptorDorsal Horn
Neuron
To Brain
Central sensitization occurs as a result of increased nociceptor drive or disinhibition after nerve injury, leading to exaggerated dorsal horn response
Disinhibition
Innocuous or Noxious Stimulus
Dorsal Horn Neuron
To Brain
Increased Nociceptor Drive
Innocuous Stimulus
Dorsal Horn Neuron
Inhibitory Input Is Downregulated
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Persistent Pain as a Disease Entity:
• Increase peripheral input: increase DH firing
• Increase firing: increased NMDA, Ca, PKC, Nitric Oxide
• Increase PKC, Ca: genetic changes
• Increase NO: decreased GABA neurons
• Increase Neurotrophins: sprouting
Cousins, MJ, 2009 AAPM
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Apkarian AV, et al. J of Neuroscience, 24(46), 2004.
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Price DD. Science 2000.
Price DD. Science. 2000;288:1769-1772.
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Price DD. Science. 2000;288:1769-1772.
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“Pain Matrix”
Moseley GL. Man Ther. 2003;8(3):130-140.
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“Pain Matrix”
• Anterior cingulate cortex (ACC)
• Insular cortex (IC)
• Thalamus
• Sensorimotor cortex (SSI, SSII)
• Cerebellum
Moseley GL. Man Ther. 2003;8(3):130-140.
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Petrovic P, et al. Science 2002;295:1737-1740.
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Petrovic P, et al. Science. 2002;295:1737-1740.
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INJURY SYMPTOMSTissue Damage
Nerve Damage
HyperalgesiaSpontaneous
Pain Allodynia
PERIPHERAL ACTIVITY
CENTRAL
SENSITIZATION
Decreased threshold to
peripheral stimuli Expansion ofReceptive field
IncreasedSpontaneous
activity
Tracey, 2008