Peripheral and Central Sensitization Flashcards
How many people does chronic pain effect in the USA
100 million
What is the annual cost for management of chronic pain in the USA
$560-635 billion
True or False:
Chronic pain has significant biological, psychological, and emotional implications
True
What is the most common location for chronic pain
Lower back
What percent of individuals with acute lower back pain will go on to develop chronic LBP
10-15%
What is the direct and indirect cost associated with the management of chronic LBP in the USA
$100-200 billion
What 2 mechanisms lead to pain becoming chronic
- Nociceptive
2. Non-nociceptive
How does the nociceptive mechanism contribute to chronic pain
Increased input from the periphery
What is increased input from the periphery considered
Central and peripheral sensitization
How does the non-nociceptive mechanism contribute to chronic pain
Cognitive processing of information
What are non-nociceptive mechanisms
Things that may amplify pain and make the pain last longer than it should
True or False:
Chronic pain occurs due to neural plasticity
True
True or False:
Peripheral sensitization has a cognitive aspect to it as well as signals sent to the brain
True
What is peripheral sensitization
Increase responsiveness and reduced threshold of nociceptive neurons in the periphery to the stimulation of their receptive fields
True or False:
peripheral sensitization can be due to alterations in ion channels
True
What can be altered about the ion channels (2)
- The number of channels
2. How long the channels are open
What is the most common alteration to the ion channels for peripheral sensitization
How long the channels are open
True or False:
There is a growing body of literature supporting the targeting of peripheral mediators to treat chronic pain states
True
What are the peripheral mediators that are targeted (3)
- Tumour necrosis factor alpha
- Cytokines
- Pro-inflammatory prostaglandins
What conditions are the peripheral mediators seen in (3)
- Tumour necrosis factor alpha: RA
- Cytokines: RA
- Pro-inflammatory prostaglandins: OA
True or False:
There are a wide range of receptors on the outside of cells
True
What do the receptors on the outside of the cell lead to
Pain, swelling, warmth, and redness
True or False:
Hyperalgesia has both peripheral and central mechanisms
True
What is hyperalgesia
Increased sensitivity to pain
What is the flare of a wound
The area where there is no direct injury but the pain spreads thre
What are the characteristics of hyperalgesia (3)
- Decreased pain threshold
- Increased pain in response to suprathreshold stimuli
- Spontaneous pain
What are the characteristics of sensitization (3)
- Decreased threshold for response
- Increased response to suprathreshold stimuli
- Spontaneous activity
Will you see hyperalgesia in the clinic
Yes’m
Where does sensitization occur
In the spinal cord itself
What do neuromodulators do
Make it easier for receptors in the periphery to respond
During the neurogenic inflammation process what occurs after tissue injury
Prostaglandins and bradykinin are released sensitizing nociceptors in the periphery
During the neurogenic inflammation process what happens when nociceptors are sensitized in the periphery
Substance P and calcitonin gene related protein (CGRP) are released
During the neurogenic inflammation process what does substance P do
Acts on mast cells releasing histamine further exciting nociceptors
During the neurogenic inflammation process what does substance P and CGRP cause the release of
Bradykinin
During the neurogenic inflammation process what does bradykinin do
Causes extravasation and blood vessel dilation
What is plasma extravasation
Fluid leaking out of blood vessels
How are TRP channels effected during the process of neurogenic inflammation
They are increased due to the increased osmolarity, pressure, and stretch
Are CGRP, substance P, histamine, and nerve growth factor (NGF) taken up by the terminal
No they stay in the tissue until they degrade or bind to something
What happens to the neuromodulators that because they aren’t taken up by the terminal
They spread to other sites in the tissue
What does the neuromodulators traveling to other sites in the tissue lead to
The wide spread effect seen during injury where there is a focal point but the tissue around the wound still hurts
What is the response to peripheral exposure of NGF (3)
- Retrograde transport of signaling endosomes
- Increased transcription of BDNF
- Central release of BNDF
What does local production of cytokines promote
Synthesis and release of NGF
What does NGF due
Binds to TrKA triggering increased excitability
What does increased excitability due to TrKA do
Promotes increased BDNF production
What does increased production of BDNF cause
Increased release from sensory terminal in CNS causing increased excitability
What is NGF good for
Neural development
What can NGF cause
Increased pain after development
NGF resulting in the release of BDNF in the CNS is an example of what type of mechanism
Central mechanism
What are the 2 mechanisms that lead enhanced excitability in the dorsal horn neurons
- Windup
2. Elevated Ca++
What causes windup
Repetitive stimulation of C-fibers
How does the response of A-delta fibers change after repetitive stimulation
The response doesn’t change it remains the same
How does the response of the C-fibers change after repetitive stimulation
There is a summation effect after each time the C-fiber is stimulated
What is the summation effect after each stimulation of the C-fiber called
Windup
What does windup lead to
Central sensitization
What does elevated Ca++ lead to
Increase glutamate release which stimulates AMPA and NMDA receptors
What does stimulating NMDA and AMPA receptors lead to
Longer depolarization of neurons
What do NK1 receptors do
Enhance the action of NMDA via second messengers
What activates NK1
Substance P
True or False:
A-delta fibers have fast membrane depolarization that is transient
True
True or False:
C-fibers have long lasting depolarization that is cumulative
True
What 2 lamina send long projections up to the thalamus
Lamina 1 and 5
True or False:
Lamina 5 sends projections back up to lamina 2
True
What does central sensitization refer to
The neurons in the dorsal horn
Is central sensitization a good or bad thing
It is somewhat of a bad thing
What does peripheral sensitization refer to
Free nerve endings in the periphery
What can nociceptor input trigger in central nociceptive pathways
A reversible yet prolonged increase in the excitability of neurons
What is central sensitization
Increased responsiveness of nociceptive neurons in the central nervous system to their normal or subthreshold afferent input
What are the symptoms associated with changes in excitability (3)
- Hypersensitivity
- Hyperalgesia
- Allodynia
What is allodynia
Increased sensitivty to non noxious stimuli
What is central sensitization maintained by (4)
- Activity dependent synaptic plasticity
- Physiologic changes in support structures
- Membrane excitability
- Gene transcription
What causes hyperalgesia in central sensitization
Alterations in nociceptors
What causes allodynia in central sensitization
Alterations in low threshold mechanoreceptors
What do people with central sensitization have hypersensitivity towards (7)
- Bright light
- Touch
- Noise
- Pesticides
- Mechanical pressure
- Medication
- Temperature (high and low)
What is causing central sensitization broad terms
Plastic changes occur in the dorsal horn due to second messengers changing the permeability and receptors on the cell membrane
What are the 3 steps of pain becoming chronic
- Activation
- Modulation
- Modification
What does the activation step lead to (2)
- Windup
2. Auto-sensitization
What causes the activation step to occur
Ion channel excitability
What does the modulation step lead to (2)
- Peripheral sensitization
2. Central sensitization
What causes the peripheral and central sensitization during the modulation step
Second messengers
How do the second messengers cause peripheral and central sensitization
They send signals back to the lamina causing an upregulation of membrane specific proteins which leads to more receptors embedded in the cell membrane
What happens during the modification step (3)
- Altered gene regulation
- Altered connectivity
- Cell death
What happens during the modulation step (1)
- Phosphorylation of receptor/ion channels
What happens during the activation step (3)
- Transduction
- Transmission
- Use-dependent augmentation
What is use-dependent augmentation
Responding with more umf
When does the modification step occur
After the tissue has healed
What does the modification step lead to
Chronic pain
How does the modification step lead to chronic pain
The inhibitory neuron cell dies and a new excitatory synapse is formed where the inhibitory neuron cell was
What sprouts from the dead inhibitory interneuron
A-beta fiber
What does the newly sprouted A-beta fiber cause
Altered cell excitation
Talk to Dr. Brown about this
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