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8/6/2019 Pa Tho Physiology of Pain
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Pathophysiology of PainPathophysiology of Pain
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Nociception
The detection of tissue damage by
specialized transducers connected to
A-delta and C-fibers
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Pain
An unpleasant sensory and
emotional experience which we
primarily associate with tissue
damage or describe in terms of such
damage, or both
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Classification of Pain
Nociception
Proportionate to the stimulation of
the nociceptor
When acute
Physiologic pain
Serves a protective function
Normal pain Pathologic when chronic
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Classification of Pain:
Neuropathic Pain
Sustained by aberrant processes in
PNS or CNS
Disproportionate to the stimulation
of nociceptor
Serves no protective function
Pathologic pain
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Normal Central Pain
Mechanisms
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Peripheral and Central Pathways for
Pain Ascending TractsAscending Tracts Descending TractsDescending Tracts
Cortex
Midbrain
Medulla
Spinal Cord
Thalamus
Pons
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Pain-Inhibitory and Pain-Facilitatory
Mechanisms Within the Dorsal Horn
A-DELTAA-BETA C
Neuronal circuitryNeuronal circuitry
within the dorsal horn.within the dorsal horn.
Primary afferent neuronPrimary afferent neuron
axons synapse ontoaxons synapse onto
spinothalamic neuronsspinothalamic neurons
and onto inhibitory andand onto inhibitory and
excitatory neurons.excitatory neurons.TO BRAIN
+ +
+_ _
+
0
STTSTTNEURONNEURON
STTSTTNEURONNEURON
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Rating of First and Second
Pain Intensity
Adapted with permission from Cooper BY, et al.Adapted with permission from Cooper BY, et al. Pain.Pain. 1986;24:1031986;24:103andandfrom Lee KH, et al. In: Fields HL, Dubnerfrom Lee KH, et al. In: Fields HL, Dubner
R, Cervero F, eds.R, Cervero F, eds. Proceedings of the Fourth World Congress on Pain.Proceedings of the Fourth World Congress on Pain. New York, NY: Raven Press;1985:204.New York, NY: Raven Press;1985:204.
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Mechanisms of Pathologic
Pain
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Mechanisms of Pathologic Pain:
General Considerations
Pain-processing mechanisms
function abnormally
Examples: neuropathic pain syndromes
Nociception is sustained by chronic
injury
Example: arthritis
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Mechanisms of Pathophysiologic
Pain: Peripheral Processes
Injured or diseased nerve(s)
Growth of axonal sprouts Formation of ectopic foci
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ec an sms o a op ys o og c
Pain:
Central Sensitization Processes
Repeated impulse activity in C
nociceptive neurons produces
sensitization of STT neurons over time Sensitization of STT neurons leads to
Increased spontaneous impulse activity
Enhanced responses to impulses innociceptive and non-nociceptive primaryafferents
Causes hyperalgesia, allodynia, and
spontaneous pain
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Temporal summation
of second pain
(second painsummation is a result
of repeated input from
C-fiber).
Temporal summation of
responses of a dorsal
horn (STT) neuron to
repeated C-fiber
stimulation and the
effects of the NMDA-receptor antagonist
ketamine.
Reproduced with permission from Price DD, et al. In: Fields HL, Liebeskind JC, eds. Pharmacological Approaches to theTreatment of Chronic Pain: New Concepts and Critical Issues. Seattle, Wash: IASP Press; 1994:66.
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Mechanism of Central Sensitization Associated
With Tonic C Nociceptor Input
Enhanced postsynaptic
effects by NMDA-
receptor sensitization
Tonic activity in
C nociceptors
A-DELTAA-BETA
TO BRAIN
+ +
+_ _
+
0
STTSTTNEURONNEURON
STTSTTNEURONNEURON
+
+++ +
C
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Intracellula
r
Mechanism
s of
Sensitizati
on
Reproduced with permission from Mao J, et
al. Pain. 1995;61:361.
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Enhanced postsynaptic
effects by NMDA-
receptor sensitization
Tonic activity in
C nociceptors
A-DELTAA-BETA
TO BRAIN
+ +
+_ _
+
0
STTSTTNEURONNEURON
STTSTTNEURONNEURON
+++ +
Loss of Inhibitory Interneuron
FunctionC
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Brain-to-Spinal-Cord
Modulation of Pain
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Pain Modulation
Mechanisms
Brain centers/pathways that
descend to the spinal cord andmodulate pain
Tail-flick test
Off-cells inhibit transmission of
pain-related information to the brain
On-cells facilitate transmission of
pain-related signals to the brain
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Pathophysiology of Pain:
Conclusion Neuronal plasticity
Nociceptor, spinal cord, brain
Pain-facilitatory and pathophysiologic
mechanisms
Wind-up phenomenon
Central sensitization
Modulating mechanisms
Ascending
Descending