Transcript pain_etiology32

Etiology and Pathophysiology
of Various Pain Syndromes
Nociception
The detection of tissue damage by
specialized transducers connected to
A-delta and C-fibers
Pain
An unpleasant sensory and emotional
experience which we primarily associate
with tissue damage or describe in terms of
such damage, or both
Classification of Pain Nociception
• Proportionate to the stimulation of the
nociceptor
• When acute
– Physiologic pain
– Serves a protective function
– Normal pain
• Pathologic when chronic
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
Classification of Pain: Mixed Pain
• Nociceptive components
• Neuropathic components
• Examples
– Failed low-back-surgery syndrome
– Complex regional pain syndrome
Classification of Pain: Idiopathic Pain
• No underlying lesion found yet, despite
investigation
• Pain disproportionate to the degree of
clinically discernible tissue injury
Normal Central Pain
Mechanisms
Peripheral and Central Pathways for Pain
Adapted with permission from Fields HL, Price DD. In: Harrington A, ed. The Placebo Effect. An Interdisciplinary
Exploration. Cambridge, Mass: Harvard University Press; 1997:106.
Pain-Inhibitory and Pain-Facilitatory
Mechanisms Within the Dorsal Horn
0
A-BETA
A-DELTA
_ _
Neuronal circuitry
within the dorsal horn.
Primary afferent neuron
axons synapse onto
spinothalamic neurons
and onto inhibitory and
excitatory neurons.
+
+
STT
NEURON
++
TO BRAIN
C
Rating of First and Second Pain Intensity
Adapted with permission from Cooper BY, et al. Pain. 1986;24:103 and from Lee KH, et al. In: Fields HL,
Dubner R, Cervero F, eds. Proceedings of the Fourth World Congress on Pain. New York, NY: Raven Press;
1985:204.
Mechanisms of
Pathologic Pain
Mechanisms of Pathologic Pain:
General Considerations
• Pain-processing mechanisms function
abnormally
– Examples: neuropathic pain syndromes
• Nociception is sustained by chronic injury
– Example: arthritis
Mechanisms of Pathophysiologic Pain:
Peripheral Processes
• Injured or diseased nerve(s)
• Growth of axonal sprouts
• Formation of ectopic foci
Mechanisms of Pathophysiologic 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 in nociceptive and
non-nociceptive primary afferents
• Causes hyperalgesia, allodynia, and
spontaneous pain
Temporal summation
of second pain
(second pain
summation 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 NMDAreceptor antagonist
ketamine.
Reproduced with permission from Price DD, et al. In: Fields HL, Liebeskind JC, eds. Pharmacological Approaches to the
Treatment of Chronic Pain: New Concepts and Critical Issues. Seattle, Wash: IASP Press; 1994:66.
Mechanism of Central Sensitization Associated
With Tonic C Nociceptor Input
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A-BETA
A-DELTA
C
Tonic activity in
C nociceptors
_ _
+
+
+
STT
++
NEURON
++
++
TO BRAIN
Enhanced postsynaptic
effects by NMDAreceptor sensitization
Intracellular
Mechanisms
of
Sensitization
Reproduced with permission from Mao J, et
al. Pain. 1995;61:361.
Loss of Inhibitory Interneuron Function
0
A-BETA
A-DELTA
Tonic activity in
C nociceptors
_ _
+
C
+
STT
NEURON
++
++
++
TO BRAIN
Enhanced postsynaptic
effects by NMDAreceptor sensitization
Brain-to-Spinal-Cord
Modulation of Pain
cell
Adapted with permission from Fields HL, Price DD. In: Harrington A, ed. The Placebo Effect. An Interdisciplinary
Exploration. Cambridge, Mass: Harvard University Press; 1997:108.
Mechanisms of Neuropathic Pain
• Noninflammatory states
• Inflammatory states
Pathophysiology of Neuropathic Pain
• Ectopic activity in the peripheral pathways,
including axons and DRG
• CNS mechanisms
Radicular and Discogenic Neuropathic Pain
Mechanisms
• Ectopic activity of the nerve root nervi nervorum
• Sensitization and ectopic activity of the
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nociceptors innervating spinal periosteal
structures, ie, annuli and ligaments
Possible role of abnormal nociceptors overgrown
within the intradiscal space, postsurgical
epidural scars, degenerated facet joints
CNS sensitization and reorganization
Neuropathic Pain: Central Mechanisms
Peripheral neuropathic events can be
complicated by temporary or long-term
CNS changes, such as central sensitization
and then reorganization of the pain
pathways at the dorsal horn level
Neuropathic Pain and SMP
• Some neuropathic pains are sustained, at least in
•
•
part, by sympathetic efferent activity
– SMP
Expression of alpha-adrenergic receptors on
injured C-fibers may be a relevant mechanism of
SMP, but others are possible
Clinical findings consistent with CRPS signal an
increased likelihood of SMP
Nociceptive Pain
Neuropathic Pain
PNS
peripheral
nervous
system
CNS
central
nervous
system
Peripheral
sensitization
“Healthy”
Abnormal
nociceptors
nociceptors
PNS
Central
CNS
Normal
transmission sensitization
Central
reorganization
Physiologic
state
Pappagallo M. 2001.
Pathologic
state
Nociceptive Pain
• Sensitization and activation of “healthy”
nociceptor endings and recruitment of
“silent” nociceptors
• “Soup” of inflammatory algogenic agents,
such as protons, prostaglandins,
bradykinin, serotonin, adenosine,
histamine, cytokines
Low Back Pain and Sciatica: Nociceptive/
Inflammatory Pain Mechanisms
• Activation and sensitization of the nerve
root nervi nervorum from root
compression/traction
• Sensitization of the nociceptors of the
annulus fibrosus, periosteal spinal
structures, and ligaments, due to acute
inflammation, eg, status post trauma
• Hyperalgesia (deep spinal and dermatomal)
due to central sensitization
Fibromyalgia Syndrome:
Pathophysiology
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Central-nervous-system abnormalities
Muscle pathology
Psychopathology
Genetic predisposition
Myofascial Pain Syndrome:
Pathophysiology
• Current pathophysiologic knowledge relies
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significantly on clinical examination
Histologic studies of trigger points have not been
particularly helpful
Local ischemic factors due to prolonged muscle
contraction may play a role in the development of
the pain
Denervation supersensitivity has been suggested
by some to be the cause
Pathophysiology of Pain: Conclusion
• Neuronal plasticity
– Nociceptor, spinal cord, brain
• Pain-facilitatory and pathophysiologic
mechanisms
– Wind-up phenomenon
– Central sensitization
• Modulating mechanisms
– Ascending
– Descending