Nonopioid Analgesics and Adjuvants

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Pathophysiology 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 PainNeuropathic 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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Classification of Pain Mixed Pain

• Nociceptive components
• Neuropathic components
• Examples
• Failed low-back-surgery syndrome
• Complex regional pain syndrome

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Classification of Pain Idiopathic Pain

• No underlying lesion found yet, despite
  investigation
• Pain disproportionate to the degree of clinically
  discernible tissue injury

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Normal Central Pain Mechanisms
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Peripheral and Central Pathways for Pain
Ascending Tracts
Descending Tracts
Cortex
Thalamus
Midbrain
Pons
Medulla
Spinal Cord
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Pain-Inhibitory and Pain-Facilitatory Mechanisms
Within the Dorsal Horn
0
C
A-DELTA
A-BETA
_ _


Neuronal circuitry within the dorsal
horn. Primary afferent neuron axons synapse onto
spinothalamic neurons and onto inhibitory and
excitatory neurons.
STTNEURON


TO BRAIN
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Rating of First and Second Pain Intensity

Adapted with permission from Cooper BY, et al.
Pain. 198624103 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 1985204.
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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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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

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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 NMDA-receptor 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 199466.
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Mechanism of Central Sensitization Associated
With Tonic C Nociceptor Input
0
A-DELTA
A-BETA
C
Tonic activity in C nociceptors
_ _



STTNEURON


Enhanced postsynaptic effects by NMDA-receptor
sensitization




TO BRAIN
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Intracellular Mechanisms of Sensitization
Reproduced with permission from Mao J, et al.
Pain. 199561361.
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Loss of Inhibitory Interneuron Function
0
C
A-DELTA
A-BETA
Tonic activity in C nociceptors
_ _


STTNEURON


Enhanced postsynaptic effects by NMDA-receptor
sensitization




TO BRAIN
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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 and modulate 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

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