Physiology of Pain Flashcards
Pain is accompanied by an
emotional reaction
Why do we feel pain?
- helps us learn to avoid harmful/dangerous
situations - prevents further injury or death
- tells us to rest and heal following
injury
Types of Pain:
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Adaptive Pain:
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Pathological Pain:
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Sensations of Pain:
- sharp stab
- deep ache
- burning
- freezing
- itch
What are nociceptors?
- primary sensory afferent neurons
- detect noxious stimuli
Nociceptors
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Nocicpetors have —– ——- —— in the periphery.
free nerve endings
Afferent Nerve Endings:
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Afferent Nerve Fiber Classification:
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When Aδ fiber nociceptor are activated, what type of pain is experienced?
sharp pricking pain
When C fiber nociceptors are activated, what type of pain is experienced?
- slow dull ache
- burning
Timing of nociceptors:
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Pain transduction occurs in
two waves; first pain which is fast and sharp and the second pain which dull and slow
Pain Transduction
- fast and sharp = A delta
- then c fibers which last longer
What activates nociceptors (4)?
- pressure
- temperature
- chemical
- tissue damage/inflammation
Which modality do c-fiber nociceptors respond to?
- most are polymodal
- respond to pressure, temp and
chemical
Nociceptors: Pressure Transduction:
- mechanically sensitive ion
channels respond to pressure - precise channels and ions not
identified - polymodal (respond to many
stimuli) - possible acid sensing
- possible transient receptor
potential channels
Nociceptors: Temperature Transduction:
- transient receptor potential family
of channels transduce different
temperatures - TRPV1 = hot = chilli is agonist
- TRPM = cold = menthol
- TRPA1 = v vold = cinnamon
What chemicals are released as part of tissue injury and inflammation?
- ATP
- H+
- serotonin from platelets
- histamine from mast cells
- bradykinin
- prostaglandins
- nerve growth factors
Prostaglandins are produced from
the conversion of arachidonic acid by COX enzymes
What is the effect of chemical released during tissue injury and inflammation on nociceptors?
excitatory effect
(begins the pain pathway)
Activation of nociceptors by inflammation:
- ATP binds to
- H+ binds to
- Serotonin binds to
- P2X
- acid sensing ion channels
- 5-HT3
binding of the above excites nociceptors
Neurogenic inflammation is
inflammation arising due to activity of neurons
Neurogenic Inflammation: Process:
- activation of one branch of a
nociceptor by inflammation,
triggers the release of substance P
and CGRP from another branch - this causes vasodilation
- and activation of mast cells
- which results in the release of
histamine - leading to increased inflammation
- contributes to the
pathophysiology of inflammatory
diseases
Hyperalgesia
noxious stimuli produce an exaggerated pain response
Allodynia
non-noxious stimuli produce a painful response
Nociceptors are modulated by
inflammation and can cause hypersensitivity
What is the purpose of pain hypersensitivity?
Pain hypersensitivity after an injury promotes healing by ensuring that there is minimum contact with the injured tissue until repair is complete
Hyperalgesia alone leads to —– sensitisation
peripheral
Continued peripheral sensitisation due to hyperalgesia leads to
central sensitisation
due to barrage of information reaching spinal cord
allodynia + hyperalgesia
Hypersensitivity:
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Is peripheral or central sensitisation a major mechanism in neuropathic pain?
Central sensitisation
Peripheral sensitisation is an increase in the responsiveness of
the peripheral ends of nociceptors
Peripheral sensitisation is driven by
tissue injury or inflammation
What chemicals are involved in peripheral sensitisation (3)?
- bradykinin
- neuron growth factor
- prostaglandins
Peripheral Sensitisation: Role of Bradykinin:
to reduce the threshold of heat activated channels (TRPV1)
Peripheral Sensitisation: Role of Neuron Growth Factors:
to reduce the threshold of heat activated channels (TRPV1)
Peripheral Sensitisation: Role of Prostaglandins:
to reduce the threshold of Na+ channels, allowing influx of Na+ to depolarise neuron leading to action potential firing
How does bradykinin act on TRPV1?
- indirectly
- bradykinin binds to a
metabotropic GPCR - leading to the activation of protein
kinase - leading to the phosphorylation of
TRPV1 - phosphorylation of TRPV1 reduces
its threshold, hence more action
potentials are fired
Nociceptive information ascends via which spinal tract?
the spinothalamic tract
What is the path of the first order neuron in the pain pathway?
- first order neurons are
nociceptors - enter the dorsal horn of grey
- synapse in the substantia
gelatinosa - collateral branch up and
downwards form the tract of
Lissauer - excites the second order neuron
Spinothalamic Tract: pathway:
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What is the path of the second order neuron in the pain pathway?
- crosses in dorsal horn at each
level (decussates just above entry level) - ascend in the anterolateral column
to the thalamus
Spinothalamic Tract: Second-order Neuron:
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Why is pain sometimes referred to different areas? eg: visceral pain as cutaneous
convergence of visceral and cutaneousq nociceptors on same second order neurons resulting in the brain perceiving visceral pain as cutaneous
What is the path of the third order neuron in the pain pathway?
- third order neurons ascend to the
primary somatosensory cortex - the third order neurons project ot the
insular cortex
In the primary somatosensory cortex the sensory component is encoded:
- tell us where it hurts and the modality
In the insular cortex the emotional component of pain is encoded:
- unpleasantness
- negative effect
Regulation of Pain in the Descending Pathway:
- higher cortical regions project to the
periaqueductal grey matter - pag projects to the rostral ventromedial
medulla - rvm projects to the dorsal horn of grey
pathway can be excitatory to increase the pain or inhibitory to decrease the pain
PAG neurons excite serotonergic neurons
those serotonergic 5HT neurons project to the dorsal horn
the release of serotonin in the dorsal horn activates inhibitory interneurons in the dorsal horn
inhibitory interneurons will release enkephalins, endorphins and dynorphins which will act on opiod receptors
results in inhibition of the second order neuron in ascending pathway
reducing the activity of second order neuron, reduces the pain information that reaches the brain, hence analgesia at this point
RVM will release noradrenaline which will be parallel and achieve the same result
The endogenous opiod system plays an important role in the pain pathway; to
inhibit pain
The endogenous opiod system can be activated by:
- the spinothalamic tract:
spinomesecephalic fibers - higher cortical regions: limbic structures,
primary somatosensory cortex
Endogenous Opiod System:
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Pain Treatment:
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