Pathophysiology of Pain

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 Ascending Tracts Descending Tracts
Cortex Thalamus Midbrain

Pons

Medulla

Spinal Cord

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

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

0
A-BETA A-DELTA C

Tonic activity in C nociceptors _ _ + + + STT ++ NEURON ++ ++

TO BRAIN

Enhanced postsynaptic effects by NMDAreceptor sensitization

Intracellula r Mechanism s of Sensitizati on

Reproduced with permission from Mao J, et al. Pain. 1995;61:361.

Loss of Inhibitory Interneuron Function

0
A-BETA A-DELTA

C Tonic activity in C nociceptors

_ _ +
STT NEURON

+ ++ ++ ++
Enhanced postsynaptic effects by NMDAreceptor sensitization

TO BRAIN

Brain-to-Spinal-Cord Modulation of Pain

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

Pathophysiology of Pain: Conclusion

Neuronal plasticity
Nociceptor, spinal cord, brain

Pain-facilitatory and pathophysiologic mechanisms

Wind-up phenomenon Central sensitization

Modulating mechanisms
Ascending Descending