Pathophysiology of the
Pain Response
Peripheral and Central Nervous
System Involvement
The Pain Response
Activation of the
Tissue Damage
Peripheral Nervous
System
Pain
Samad TA et al. Nature. 2001;410:471-5.
The Pain Pathway
Pain Perception
Brain
Spinal Cord
Nociceptor Gottschalk A et al. Am Fam Physician. 2001;63:1979-84.
Fields HL et al. Harrison’s Principles of Internal Medicine. 1998:53-8.
Central Pain Transmission
Nociceptors
• Nociceptors process and transmit painful
stimulation to CNS
• Mostly C and Aδ fibers
• C fibers unmyelinated and activated by chemical,
thermal and mechanical stimulation
• Aδ fibers are myelinated and are 25 X faster than C
fibers
• Mechanical and thermal activation
• Somatic structures rich in Aδ fibers and C fibers vs
visceral structures with mostly C fibers
• Aδ fibers allows rapid precise location of injury
• Pain from C fibers more dull, ill-defined and longer
lasting
Neuronal Plasticity and Pain
Peripheral Activation Central
Autosensitization Windup
Modulation
Modification
VR1
Voltage-Gated
•Heat
External Ca2+
Sodium Channels
•Mechanical
Stimuli •Chemical
Action Potentials
External Stimulus
VR1
HEAT
PKA
Sensitizing Stimulus EP
Receptor SNS/PN3
PGE2
PKCε TTX-Resistant
Sodium
Bradykinin Channel
BK
Receptor
Glutamate
(-)
P
NMDA
Substance P
P
AMPA
Ca2+
(+) Dorsal Horn Neuron
(+) PKC
8 Hyperalgesia Normal
Pain
Pain Intensity
Response
6 Injury
Allodynia
Hyperalgesia—heightened
4 sense of pain to noxious
stimuli
2 Allodynia—pain resulting
from normally painless
stimuli
0
Stimulus Intensity
Nociceptors
Skin
Aβ -fibers
* = Ectopic activity
Prostaglandins Prostaglandins
COX-2
Pain
COX-2
EP PKA
Receptor PKCε
PGE2
P
Resting
SNS/PN3
Membrane
TTX-Resistant Potential
Sodium Increases
Channel
Neuron Firing
Threshold
Decreases
Prostaglandins Prostaglandins
COX-2
Pain
NMDA (-)
P
Substance P
AMPA P
Ca2+
(+) Dorsal Horn Neuron
(+) PKC
GABA
Glutamate Glycine
(-)
NMDA
P
Substance P
AMPA P
Ca2+
(+) Dorsal Horn Neuron
(+) PKC