Beruflich Dokumente
Kultur Dokumente
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Elon Eisenberg MD
• Nociceptive pain
• Inflammatory pain
• Neuropathic Pain
• “Dysfunctional” pain
Nociceptive pain
• A useful, protective, adaptive feature of the
sensory nervous system.
• Transduction
• Transmission
• Modulation
Pain Transduction
Nociceptors
• Free nerve endings
• High threshold
• Polymodal
• Receptive fields
Pain Transmission
Pain Transmission
A-delta C fibers
Myelinated Unmyelinated
1.0-35 m/s 0.3-1.0 m/s
First pain Second pain
Sharp pain Dull pain
Synaptic Transmission
Pain
Nociception
C-fiber +
Light touch
WDR
Aβ-fiber _
P
Primary afferent Spinal cord
A
Descending Pathways
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Pain Modulation
• Trauma
• Diagnostic procedures
• Surgery
• Labor
Nociceptive Pain - Potential Interventions
• Neural blocks
- Peripheral
- Central
• General anesthesia
• Pain modulation
- Local stimulation
- Opioids
Nerve Blocks
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Epidural Blocks
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Nociceptive Pain - Summary
• Nociceptive pain results from the exposure of high
threshold primary sensory neurons in the periphery to
noxious stimuli
• The sensory neurons express highly specialized
transduction proteins that detect extreme temperature,
irritant chemical, intense mechanical stimuli and
convert them into electrical activity.
• The resulting pain is perceived within milliseconds
and dissipates quickly with the removal of the stimulus.
Inflammatory Pain ((1
• Pain that is associated with tissue damage and
active inflammation.
• The inflammatory response recruits and activates
leukocytes, which produce inflammatory mediators,
cytokines, and chemokines – that a alter neuronal
sensitivity.
• This sensitization process occurs over a period of
seconds to days from the initial tissue damage.
•Sensitization lowers the activation threshold of
nociceptors.
Inflammatory Pain ((2
• This results in spontaneous pain, allodynia and
hyperalgesia.
• Molecules associated with inflammation may also
change gene expression levels within nociceptors
leading to altered transmitters, receptors, or ion
channels (phenotypic changes)
• Additionally, central sensitization – a state of
enhanced excitability in the spinal cord in which
peripheral inputs to the CNS are amplified –also
occurs. This contributes to pain sensitivity outside
of the area of damage (secondary hyperalgesia)
Sensitization of Primary Afferent
Substance P
Cytokines
K
+
Prostaglandines
Free radicals
Inflammation-Induced Phenotypic Changes
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Substance P
CGRP
Glutamate
Cytokines
Free radicals
K
+
Central Sensitization
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25
20
15
10
5
0
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60
Time
35
30
Pain Index
25
20
15
10
NSAID/ 0
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60
NMDA
ant. Time
Injection
• Post-operative pain
• Rheumatoid arthritis
• Infection (i.e. ear)
• Pancreatitis
Inflammatory Pain - Potential Interventions
• Anti-inflammatory drugs
• Steroids
• Free radical scavengers
• Substance P blocking agents
• Pain modulation
Neuropathic Pain
• Is a combination of pain and loss of function that
originates from damage to the nervous system.
• In contrast to nociceptive pain, there is no change
in nociceptive transduction sensitivity at the
periphery.
• Rather, a series of profound changes occur at
multiple levels of the nervous system.
Neuropathic Pain: Signs & symptoms:
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• Spontaneous pain
• Hyperalgesia / allodynia
• Loss of sensation
Post-Mastectomy Pain Syndrome
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Intercosto-brachial nerve
Post Herpetic Neuralgia
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(Chronic Constrictive Injury (CCI
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Neuropathic Pain Mechanisms
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Na+ channel
expression Primary excitatory afferent nerve fiber
increased
Na+ = sodium ion. England et al. Neurology 1996;47:272-76. Ochoa et al. Brain. 1980;103:835-853
Taylor. Curr Pain Headache Rep. 2001;5:151-161. Sukhotinsky et al. Eur J Pain. 2004;8(2):135-43
Ectopic Discharge
Central Sensitization
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++
Ca
Central
sensitization
Pain
Nociception
C-fiber +
Light touch
WDR
Aβ-fiber _
P
Primary afferent Spinal cord
A
Spinal Cord Reorganization
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NE
Theoretical Representation
Allodynia in CRPS
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Dysfunctional Pain
• Much less is known about it.
• Heightened pain sensitivity in the absence of
noxious stimuli, peripheral pathology or
inflammation, and lesion to the nervous system.
• Abnormal function of intact nervous system.
• Includes: fibromyalgia, tension-type headaches,
IBS, and migraine.
…Wrong Object
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Dysfunctional Pain
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Thank You