Pain Mechanisms Flashcards
What is pain?
An unpleasant, sensory and emotional experience
Associated with tissue damage
Or described in the terms of such damage
What are the three main forms of pain?
Nociceptive pain
Inflammatory pain
Pathological pain
Describe nociceptive pain
Adaptive
Short lived
Immediate response
Describe inflammatory pain
Adaptive
Assists in heling
Persists over days or weeks
Describe pathological pain
Maladaptive
No physiological purpose
Persists over months, years or more
How may people in the UK suffer from chronic pain?
Half a million
How does pain originating from the skin present?
Well localised
Pricking
Stabbing
Burning pains
How does pain originating in the muscle present?
Poorly localised Aching Soreness Tender Cramping
How does pain originating in the viscera present?
Poorly localised, often referred
Dull, vague
Feelings of fullness and nausea
Outline the somatosensory pathways
Pain picked up by sensory receptor
Processed in primary afferent neurons
Passed to the 2nd and then 3rd order projection neurons
Then the somatosensory cortex
Where are primary afferent neurons located?
DRG for limbs trunk and lower back
Crania ganglia for the face and anterior head
Where are 2nd order somatosensory neurons found?
In the dorsal horn of the spinal cord
And in brainstem nuclei
Where are the 3rd order somatosensory neurons found?
Thalamic nuclei
What is different about the processing of pain from joints?
Only a two neuron chain which relays to the cerebellum
Which exceptions exist to the normal somatosensory pathways?
Spinal cord reflexes
Proprioception
What are nociceptors?
Specific peripheral primary sensory afferent neurons for pain
What is the normal structure of a nociceptor?
Pseudounipolar
What does a neuron being pseudo-unipolar mean?
Single process from the cell body which splits into two axons
Through which method of transmission do 2nd and 3rd order neurons communicate?
Chemical synapse transmission
What is the purpose of nociceptive pain?
Warning to detect and deter from damaging stimuli
Also homeostatic to “toss and turn” in bed to prevent MSK pain
Describe the intensity threshold for nociceptor activation?
High
Why is nociceptive pain necessary?
Act as warning
And alert to tissue damage
Which reflexes does nociceptive pain initiate?
Flexion.withdrawal
Why is there an emotional component to pain?
To prevent aversive memories to stop you doing the painful thing again
What is the common cause of inflammatory pain?
Infection
What are the main features of inflammatory pain?
Hypersensitivity
Allodynia
Define hypersensitivity
Heightened sensitivity to normal noxious stimuli
What is allodynia?
Sensation on pain brought on by non-noxious stimuli
Why is inflammatory pain important?
Assists in healing by discouraging physical contact/movement of the damaged body part
What is the purpose of pathological pain?
None
What is neuropathic pain?
Due to an injury of a pathway so stimulus is abnormally processed
What is dysfunctional pain?
No inflammation or damage
But positive symptoms anyways
What process appears to occur randomly in dysfunctional pain?
Mechanoreceptors and other peripheral neurons for non-noxious stimuli suddenly change function
Start sending nociceptive pain signal
What are the subtypes of nociceptor?
A-delta
C-fibres
Describe A-delta nociceptors
For mechanical/thermal nociceptors
Thinly myelinated
Mediate first/fast pain
Describe C-fibres
Polymodal
Unmyelinated
Mediate second/slow pain and long-lasting pain
Which is bigger A-delta or C-fibre?
A-delta
What does being “polymodal” mean?
Respond to all types of stimulus
What is frequency coding?
Rate of action potential firing is directly proportional to the intensity of the stimuli
What are the 3 subclasses of A-delta fibre?
A-MH (I)
A-MH (II)
A-M
Describe the A-MH (I) subclass of A-delta receptor
Respond to strong mechanical stimuli
Respond to noxious heat >53C
What may cause the threshold of intensity of stimuli to decrease on the A-MH (I) receptor?
Injury
Describe A-MH (II) subclass of A-delta fibres
Respond to noxious mechanical stimuli
Respond to heat 43-47C
Mediate first pain to heat
Which type of A-delta fibres are sensitive to capsaicin?
A-MH (II)
What do A-M A-delta fibres respond to?
noxious mechanical stimuli
What are the 4 types of C fibre?
C-MH
C-M
C-H
C-MiHi
Describe C-MH fibres?
Respond to noxious mechanical stimuli
Activated by noxious heat (39-51C)
Sensitise to repeated stimuli
Contribute to the localisation of pain
What do C-M fibres respond to?
Mechanical stimuli
What do C-H fibres respond to?
Noxious heat 42-48C
What do C-H fibres mainly mediate?
Hyperalgesia
In which situation do C-H fibres become sensitive to mechanical stimuli?
Inflammation
What are C-MiHi fibres sensitive to under normal circumstances?
Nothing (silent receptors)
In which situation do C-MiHi fibres become sensitive to heat and mechanical stimuli?
Inflammation
Which types of C-fibres are sensitive to capsaicin?
C-MH
C-MiHi
Which receptors sense H+ in acid?
ASIC
Which receptors are activated by ATP?
P2X
Which receptors are activated by bradykinin?
B2
What are petidergic polymodal nociceptors?
Subclass of C fibres Which have afferent and efferent functions to carry noxious stimuli
Outline the afferent function of the petidergic polymodal nociceptors
Tranmits nociceptive info to the CNS
Via the release of glutamate and other peptides (such as substance P, neurokinin A)
Outline the efferent function of polymodal peptigergic nociceptors
Release pro-inflammatory mediates from the peripheral terminals
(eg CGRP and substance P)
Contributes to neurogenic inflammation
Outline normal synaptic transmission events in the synaptic terminal
AP comes and depolarises the pre-synaptic terminal membrane
Causes Ca2+ influx via VGCCs
Vesicles then move to and fuse with the presynaptic membrane and release GLU into the synapse
Outline the normal post-synaptic events in the post-synaptic terminal
AMPAR activation leads to depol of post-synaptic neuron
Relieve Mg2+ block on NMDAR
Ca2+ influx
AP continues
Which receptors are responsible for the fast part of synaptic transmission?
AMPAR
Which receptors are responsible for the slow, long lasting part of synaptic transmission?
NMDAR
What does the neuropeptide release on intense synaptic activity cause?
slow EPSP
Further alleviation of Mg2+ NMDR block and further activation of NMDAR
In which Laminae of Rexed do the C-fibres terminate in?
I and outer portion of II
Where are signals from the Laminae of Rexed transmitted to?
Wide dynamic range neuron
In which laminae of Rexed do A-delta signals terminate in?
I and II
Where do A-beta fibres synapse?
In Laminae III-V
Why is there room for error in signal processing on the WDRN?
WDRN receives 3 diff typs of info
Brain doesn’t know what type it is - just aware that the WDRN is active
Matches this with the laminae active to assess signal type
Outline peripheral sensitisation of nociceptors
Mediated on site
Requires ongoing peripheral pathology to keep up
Causes primary hyperalgesia
How does peripheral sensitisation cause hyperalgesia?
Reduced threshold and amplified response
Why could continued pain cause analgesia instead of hyperalgesia?
Neurons die and then cannot sense the pain
Describe central sensitisation
Increase in CNS neuron activity
Underlies pain persisting after tissue healing
Major role in mechanical sensitisation
Causes secondary hyperalgesia
How does central sensitisation cause secondary hyperalgesia?
Recruits various input to nociceptive pathways
Abnormally processing of sensory input occurs
What may trigger visceral pain?
Stretching, twisting, inflammation and ischaemia
Not burning or cutting
Where do visceral pain signals synapse?
Laminae I and V
How do visceral pain signals enter the CNS?
Follow sympathetic pathways to enter the dorsal horn
Or some converge on the spinothalamic neurons
Describe viscerosomatic pain
Sharp and well localised pain
Occurs when inflammatory exudate from a disease organ comes into contact with body wall
What are the main two major nociceptive tracts?
Spinothalamic tract
Spinoreticular tract
Where does the spinothalamic tract originate?
Lamina I
Outline the spinothalamic tract
Projection neurons in lamina I terminating in the posterior nucleus of the thalamus
Projections from lamina V (WDRN) and terminate in the posterior and ventroposterior nuclei of thalamus
Pain perception on requires signalling in one of the spinothalamic tract pathways
T/F
F
Needs to be in both to perceive pain
What does the spinoreticular tract transmit?
Largely C fibre pain
Other than the thalamus, which structures does the spinoreticular tract make connections with?
PAG
Parabrachial nucleus
Which component of pain is the spinoreticular tract involved in?
Emotional component
Fear, arousal, etc
Compare pain and nociception
Nociception is the activation of nociceptors by noxious stimuli
Pain is the awareness of such suffering (which does not always match signal strength)
What is gate control theory?
Inhibitory and excitatory influences both act on the neurons in the substantia gelatinosa
When excitation > inhibition, pain is perceived
Which pain treatment makes use of this gate control system?
TENS
Which type of fibres does TENS treat?
A-beta
What can influence the spinal gate other than the stimuli received to the projection neuron?
Cognitive - focus/interpretation of pain
Emotional state
Behavioural personality
TENS treatment activates neurons in which lamina?
II
What does activation of the PAG cause?
Intense analgesia
Which structure does morphine excite?
locus coeruleus
What activates the nucleus raphe magnus?
PAG activation
Through which mechanisms is nociceptive transmission inhibited in the dorsal horn?
Direct presynaptic inhibition
Direct post-synaptic inhibition
Indirect inhibition
Explain direct presynaptic inhibition in the dorsal horn
GPCRs work to suppress VGCC opening
So inhib NTM release form nociceptors
Explain indirect inhibition in the dorsal horn
Activation of the inhibitory interneurons
Suppresses pre and post synaptic mechanisms
Explain direct post-synaptic inhibition in the dorsal horn
Works via GPCRs opening K+ channels in the projection neuron
Which transmitters are involved in indirect inhibition?
GABA
Enkephalins
