Physiology of Pain Flashcards
1
Q
What is pain?
- ‘it’s an unpleasant sensory experience associated with tissue damage”
- Pain is accompanied with an … reaction
- E.g.
A
- ‘it’s an unpleasant sensory experience associated with tissue damage”
- Pain is accompanied with an emotional reaction
- E.g. negative effect, fear, anxiety
2
Q
Why do we feel pain?
- So we can avoid … situations e.g. elicits … reflexes
- Prevents further injury or …
- Tells us to … following injury
A
- So we can avoid harmful situations e.g. elicits withdrawal reflexes
- Prevents further injury or death
- Tells us to rest following injury
3
Q
People without sensation of pain - mutation in the … channel found on our pain nerve fibres - nociceptors - don’t know when they are … tissues
A
People without sensation of pain - mutation in the sodium channel found on our pain nerve fibres - nociceptors - don’t know when they are injuring tissues
4
Q
What are the sensations of pain?
A
5
Q
Pain mechanisms
- The mechanism of pain are very complicated
- … and … components
A
- The mechanism of pain are very complicated
- Peripheral and central components
6
Q
Classification of pain
- …:
- normal functioning of nociceptors
- In response to tissue injury
- …:
- Pain in response to injury to the nervous system
A
- Nociceptive:
- normal functioning of nociceptors
- In response to tissue injury
- Neuropathic:
- Pain in response to injury to the nervous system
7
Q
Classification of pain
- Nociceptive:
- normal functioning of nociceptors
- In response to … injury
- Neuropathic:
- Pain in response to injury to the … …
A
- Nociceptive:
- normal functioning of nociceptors
- In response to tissue injury
- Neuropathic:
- Pain in response to injury to the nervous system
8
Q
Nociceptors
- Nociceptors are primary … neurons that detect …
- Pseudounipolar neurons that have one long single axon, which has a peripheral part and a central part
A
- Nociceptors are primary sensory neurons that detect pain
- Pseudounipolar neurons that have one long single axon, which has a peripheral part and a central part
9
Q
Nociceptors
- Nociceptors are primary … neurons that detect pain
- … neurons that have one long single axon, which has a peripheral part and a central part
A
- Nociceptors are primary sensory neurons that detect pain
- Pseudounipolar neurons that have one long single axon, which has a peripheral part and a central part
10
Q
Afferent nerve fibre classification
- Sensory nerve fibres can be classified by diameter and myelin content
- Aalpha and Abeta: 30-75m/sec
- Myelinated?
- … diameter
- Light touch, proprioception
- Adelta fibre - 5-30m/sec
- Myelinated?
- … diameter
- Light touch, temperature, nociception
- C fibre - 0.5-2m/sec
- Myelinated?
- … diameter
- Temperature, nociception
A
- Sensory nerve fibres can be classified by diameter and myelin content
- Aalpha and Abeta: 30-75m/sec
- Myelinated
- Large diameter
- Light touch, proprioception
- Adelta fibre - 5-30m/sec
- Thinly myelinated
- Medium diameter
- Light touch, temperature, nociception
- C fibre - 0.5-2m/sec
- Unmyelinated
- Small diameter
- Temperature, nociception
11
Q
Afferent nerve fibre classification
- Sensory nerve fibres can be classified by diameter and myelin content
- Aalpha and Abeta: 30-75m/sec
- Myelinated
- Large diameter
- Light touch, p…
- Adelta fibre - 5-30m/sec
- Thinly myelinated
- Medium diameter
- Light touch, t…, n…
- C fibre - 0.5-2m/sec
- Unmyelinated
- Small diameter
- …, …
A
- Sensory nerve fibres can be classified by diameter and myelin content
-
Aalpha and Abeta: 30-75m/sec
- Myelinated
- Large diameter
- Light touch, proprioception
-
Adelta fibre - 5-30m/sec
- Thinly myelinated
- Medium diameter
- Light touch, temperature, nociception
-
C fibre - 0.5-2m/sec
- Unmyelinated
- Small diameter
- Temperature, nociception
12
Q
which afferent nerve fibre recognise pain?
A
13
Q
… delta and … fibres that transmit pain information up towards your spinal cord
A
Alpha delta and C fibres that transmit pain information up towards your spinal cord
14
Q
Afferent nerve endings
- Nociceptors have … nerve endings in the periphery
- A-… fibres - very specialised nerve endings
- Meisner’s corpuscle - responds to very light stroking of the skin of fluttering across the surface of the skin
- Pacinian corpuscle - responds to vibration
- Ruffini ending - responds to a stretching of the skin
- Under surface - merkel discs - very light, fine touch
- A-… or …-fibres
- Quite different
- Arborise
- Endings - free endings within tissue
- No specialised organelles at peripheral termina
- A-… fibres - very specialised nerve endings
A
- Nociceptors have free nerve endings in the periphery
- A-beta fibres - very specialised nerve endings
- Meisner’s corpuscle - responds to very light stroking of the skin of fluttering across the surface of the skin
- Pacinian corpuscle - responds to vibration
- Ruffini ending - responds to a stretching of the skin
- Under surface - merkel discs - very light, fine touch
- A-delta or C-fibres
- Quite different
- Arborise
- Endings - free endings within tissue
- No specialised organelles at peripheral termina
- A-beta fibres - very specialised nerve endings
15
Q
Afferent nerve endings
- Nociceptors have free nerve endings in the periphery
- A-beta fibres - very specialised nerve endings
- … corpuscle - responds to very light stroking of the skin of fluttering across the surface of the skin
- … corpuscle - responds to vibration
- … ending - responds to a stretching of the skin
- Under surface - … discs - very light, fine touch
- A-delta or C-fibres
- Quite different
- Arborise
- Endings - free endings within tissue
- No specialised … at peripheral termina
- A-beta fibres - very specialised nerve endings
A
- Nociceptors have free nerve endings in the periphery
- A-beta fibres - very specialised nerve endings
- Meisner’s corpuscle - responds to very light stroking of the skin of fluttering across the surface of the skin
- Pacinian corpuscle - responds to vibration
- Ruffini ending - responds to a stretching of the skin
- Under surface - merkel discs - very light, fine touch
- A-delta or C-fibres
- Quite different
- Arborise
- Endings - free endings within tissue
- No specialised organelles at peripheral termina
- A-beta fibres - very specialised nerve endings
16
Q
Nociceptor responses
- What does it feel like when nociceptors are activated?
- A-delta - … pricking pain
- C-fibres - slow … ache, … pain
A
- What does it feel like when nociceptors are activated?
- A-delta - sharp pricking pain
- C-fibres - slow dull ache, burning pain
17
Q
Nociceptor responses
- What does it feel like when nociceptors are activated?
- … - sharp pricking pain
- … - slow dull ache, burning pain
A
- What does it feel like when nociceptors are activated?
- A-delta - sharp pricking pain
- C-fibres - slow dull ache, burning pain
18
Q
Unmyelinated (…) nociceptors mediate the burning pain from noxious heat stimuli and pain from prolonged mechanical stimuli.
A
Unmyelinated (C-fiber) nociceptors mediate the burning pain from noxious heat stimuli and pain from prolonged mechanical stimuli.
19
Q
… … fibers carry sharp/pricking pain
A
A deltafibers carry sharp/pricking pain
20
Q
In the lab… (sensory nerve fibres - pain)
- Recordings can be made from all sensory fibre types in a whole nerve
- Whole sensory nerve - stimulate one end - record AP at other end
- Time following the electrical stimulation - x axis
- Voltage - y axis - amplitude of signal at the recording electrodes - essentially equivalent to number of AP
- Oscilloscope - at your recording electrodes - you get a trace that looks like ^
- Compound AP - sum of all AP arriving at your recording electrode
- First of all - very fast very tall peak, corresponds to the arrival of all a-alpha and a-beta nerve fibres AP arriving at recording electrodes - first to arrive
- Second peak - a-delta fibres being stimulated - AP arrival
- Third peak - very long, drawn out, low peak - C-fibre response - conduct much slower - 1m/s - much longer for AP to arrive at the recording electrodes
- 3 peaks overall - Peak looks relatively small for C - but … C-fibres than other nerve fibres
A
- Recordings can be made from all sensory fibre types in a whole nerve
- Whole sensory nerve - stimulate one end - record AP at other end
- Time following the electrical stimulation - x axis
- Voltage - y axis - amplitude of signal at the recording electrodes - essentially equivalent to number of AP
- Oscilloscope - at your recording electrodes - you get a trace that looks like ^
- Compound AP - sum of all AP arriving at your recording electrode
- First of all - very fast very tall peak, corresponds to the arrival of all a-alpha and a-beta nerve fibres AP arriving at recording electrodes - first to arrive
- Second peak - a-delta fibres being stimulated - AP arrival
- Third peak - very long, drawn out, low peak - C-fibre response - conduct much slower - 1m/s - much longer for AP to arrive at the recording electrodes
- 3 peaks overall - Peak looks relatively small for C - but more C-fibres than other nerve fibres
21
Q
Pain Transduction
- Two pain responses:
- Fast … pricking pain
- … localised
- Activation of reflex arcs
- Activation of a-delta fibres - … pain response
- Slow … ache
- … localised
- Activation of c-fibres - last peak on trace - … pain response - much slower
- Fast … pricking pain
- Visceral pain - no first response - innervated by C-fibres, not a-delta fibres
A
- Two pain responses:
- Fast sharp pricking pain
- Well localised
- Activation of reflex arcs
- Activation of a-delta fibres - first pain response
- Slow dull ache
- Poorly localised
- Activation of c-fibres - last peak on trace - second pain response - much slower
- Fast sharp pricking pain
- Visceral pain - no first response - innervated by C-fibres, not a-delta fibres
22
Q
Pain Transduction
- Two pain responses:
- Fast sharp pricking pain
- Well localised
- Activation of reflex arcs
- Activation of …-… fibres - first pain response
- Slow dull ache
- Poorly localised
- Activation of …-… - last peak on trace - second pain response - much slower
- Fast sharp pricking pain
- … pain - no first response - innervated by …-…, not …-… fibres
A
- Two pain responses:
- Fast sharp pricking pain
- Well localised
- Activation of reflex arcs
- Activation of a-delta fibres - first pain response
- Slow dull ache
- Poorly localised
- Activation of c-fibres - last peak on trace - second pain response - much slower
- Fast sharp pricking pain
- Visceral pain - no first response - innervated by C-fibres, not a-delta fibres
23
Q
Visceral pain - no first response - innervated by …-fibres, not … fibres
A
Visceral pain - no first response - innervated by C-fibres, not a-delta fibres
24
Q
Activation of nociceptors:
- P…
- Heat
- C…
- C…
- Tissue …/…
A
- Pressure
- Heat
- Cold
- Chemical
- Tissue damage/inflammation
25
Q
- Most c-fibre nociceptors are polymodal - respond to:
- Respond to …, … and …
A
- Most c-fibre nociceptors are polymodal - respond to:
- Respond to pressure, temperature and chemical
26
Q
Polymodal nociceptors
- Most …-fibre nociceptors are polymodal - respond to:
- Respond to pressure, temperature and chemical, but in our brain - each feels …
- “our ability to distinguish pain sensations resulting from heat, cold or pressure must involve decoding within the central nervous system” - Julius & Basbaum, 2001
- how do we distinguish between them?
A
- Most c-fibre nociceptors are polymodal - respond to:
- Respond to pressure, temperature and chemical, but in our brain - each feels different
- “our ability to distinguish pain sensations resulting from heat, cold or pressure must involve decoding within the central nervous system” - Julius & Basbaum, 2001
- how do we distinguish between them?
27
Q
Moreover, because most nociceptors are …, our ability to distinguish pain sensations resulting from heat, cold or pressure must involve decoding of nociceptive signals within the … … ….
A
Moreover, because most nocicep- tors are polymodal, our ability to distinguish pain sensations resulting from heat, cold or pressure must involve decoding of nociceptive signals within the central nervoussystem.
28
Q
Pressure transduction
- … sensitive … channels respond to pressure
- Precise … not yet identified (possibly acid sensing ion channels, transient receptor potential channels)
A
- Mechanically sensitive ion channels respond to pressure
- Precise channels not yet identified (possibly acid sensing ion channels, transient receptor potential channels)
29
Q
Temperature transduction
- … … potential … of channels transduce different temperatures - large group of channels that detect different temperatures
A
-
Transient receptor potential family of channels transduce different temperatures - large group of channels that detect different temperatures
- Detect different temperatures
30
Q
Temperature transduction
- Transient receptor potential family of channels transduce different temperatures - large group of channels that detect different temperatures
- Detect different temperatures
A
- Transient receptor potential family of channels transduce different temperatures - large group of channels that detect different temperatures
- Detect different temperatures
31
Q
TRPV1 - temp is … - agonist is …
A
32
Q
TRPM - temp is … - agonist is …
A
33
Q
TRPA1 - temp is … - agonist is …
A
34
Q
Inflammation and tissue injury
Chemicals released as part of tissue injury and inflammation have … effects on …
A
- Chemicals released as part of tissue injury and inflammation have excitatory effects on nociceptors
35
Q
Activation of nociceptors by inflammation
- For example, …, protons and … can activate nociceptors
A
- For example, ATP, protons and serotonin can activate nociceptors
37
Q
Neurogenic inflammation
- Activation of one branch of a nociceptor by inflammation, triggers the release of substance … and … gene related peptide (CGRP) from another
- This causes: Vasodilation, activation of mast cells - release of … leading to more inflammation (Neurogenic inflammation)
- Contributes to … of inflammatory diseases
A
- Activation of one branch of a nociceptor by inflammation, triggers the release of substance P and calcitonin gene related peptide (CGRP) from another
- This causes: Vasodilation, activation of mast cells - release of histamine leading to more inflammation (Neurogenic inflammation)
- Contributes to pathophysiology of inflammatory diseases
38
Q
Neurogenic inflammation
- Activation of one branch of a nociceptor by inflammation, triggers the release of … P and calcitonin … related … (CGRP) from another
- This causes: …, activation of … cells - release of histamine leading to more inflammation (Neurogenic inflammation)
- Contributes to … of inflammatory diseases
A
- Activation of one branch of a nociceptor by inflammation, triggers the release of substance P and calcitonin gene related peptide (CGRP) from another
- This causes: Vasodilation, activation of mast cells - release of histamine leading to more inflammation (Neurogenic inflammation)
- Contributes to pathophysiology of inflammatory diseases
39
Q
Modulation of nociceptors by inflammation
- Inflammation can modulate nociceptors and cause …
- Important terms:
- … - Noxious stimuli produce an exaggerated pain response - Pain is worse
- … - Non-noxious stimuli produce a painful response
A
- Inflammation can modulate nociceptors and cause hypersensitivity
- Important terms:
- Hyperalgesia - Noxious stimuli produce an exaggerated pain response - Pain is worse
- Allodynia - Non-noxious stimuli produce a painful response
40
Q
Modulation of nociceptors by inflammation
- Inflammation can modulate … and cause hypersensitivity
- Important terms:
- Hyperalgesia - … stimuli produce an … pain response - Pain is worse
- Allodynia - …-… stimuli produce a painful response
A
- Inflammation can modulate nociceptors and cause hypersensitivity
- Important terms:
- Hyperalgesia - Noxious stimuli produce an exaggerated pain response - Pain is worse
- Allodynia - Non-noxious stimuli produce a painful response
43
Q
Mechanisms of pain hypersensitivity
- Peripheral and central sensitisation lead to hypersensitivity
- Peripheral sensitization - activated by inflammation at the peripheral terminals
- Lead to … - primary … - at injury site
- Central sensitization - spinal cord
- Lead to … as well as secondary … - away from primary injury site
- This is a major mechanism in … pain
- Peripheral sensitization - activated by inflammation at the peripheral terminals
A
- Peripheral and central sensitisation lead to hypersensitivity
- Peripheral sensitization - activated by inflammation at the peripheral terminals
- Lead to hyperalgesia - primary hyperalgesia - at injury site
- Central sensitization - spinal cord
- Lead to allodynia as well as secondary hyperalgesia - away from primary injury site
- This is a major mechanism in neuropathic pain
- Peripheral sensitization - activated by inflammation at the peripheral terminals
44
Q
Mechanisms of pain hypersensitivity
- … and … sensitisation lead to hypersensitivity
- … sensitization - activated by inflammation at the peripheral terminals
- Lead to hyperalgesia - primary hyperalgesia - at injury site
- … sensitization - spinal cord
- Lead to allodynia as well as secondary hyperalgesia - away from primary injury site
- This is a major mechanism in neuropathic pain
- … sensitization - activated by inflammation at the peripheral terminals
A
- Peripheral and central sensitisation lead to hypersensitivity
- Peripheral sensitization - activated by inflammation at the peripheral terminals
- Lead to hyperalgesia - primary hyperalgesia - at injury site
- Central sensitization - spinal cord
- Lead to allodynia as well as secondary hyperalgesia - away from primary injury site
- This is a major mechanism in neuropathic pain
- Peripheral sensitization - activated by inflammation at the peripheral terminals
46
Q
Peripheral sensitization
- Peripheral sensitisation is an … in the responsiveness of the peripheral ends of nociceptors’
- Driven by tissue … or …
- Bradykinin and NGF - bind to receptors of peripheral terminals and reduce the threshold of activation of … channels - … activated
- … - produced by the conversion of arachidonic acid by COX enzymes ( cyclooxygenase enzymes) will bind to receptors on the peripheral terminals of nociceptors and they reduce the threshold of sodium channels
A
- Peripheral sensitisation is an increase in the responsiveness of the peripheral ends of nociceptors’
- Driven by tissue injury or inflammation
- Bradykinin and NGF - bind to receptors of peripheral terminals and reduce the threshold of activation of TRPV1 channels - heat activated
- Prostaglandins - produced by the conversion of arachidonic acid by COX enzymes ( cyclooxygenase enzymes) will bind to receptors on the peripheral terminals of nociceptors and they reduce the threshold of sodium channels
47
Q
Peripheral sensitization
- Peripheral sensitisation is an … in the responsiveness of the peripheral ends of nociceptors’
- Driven by tissue … or …
- … and … - bind to receptors of peripheral terminals and reduce the threshold of activation of TRPV1 channels - heat activated
- Prostaglandins - produced by the conversion of arachidonic acid by COX enzymes ( cyclooxygenase enzymes) will bind to receptors on the peripheral terminals of nociceptors and they reduce the threshold of … channels
A
- Peripheral sensitisation is an increase in the responsiveness of the peripheral ends of nociceptors’
- Driven by tissue injury or inflammation
- Bradykinin and NGF - bind to receptors of peripheral terminals and reduce the threshold of activation of TRPV1 channels - heat activated
- Prostaglandins - produced by the conversion of arachidonic acid by COX enzymes ( cyclooxygenase enzymes) will bind to receptors on the peripheral terminals of nociceptors and they reduce the threshold of sodium channels
50
Q
Mechanisms of action of bradykinin
- Bradykinin can alter sensitivity of the … receptor
- Lying in … too long - Tissue damage
- Lots of inflammatory cells floating around region of damage - pumping out bradykinin
- Binds to receptor on … terminals of nociceptor
- Bradykinin receptor - metabotropic G coupled protein receptor
- Bradykinin binds to it - activates… protein - activates secondary messengers
- Activates protein kinases -> phosphorylate TRPV1 channel
- Reduces threshold - fires more easily
- That is … sensitisation leading to primary hyperalgesia
A
- Bradykinin can alter sensitivity of the TRPV1 receptor
- Lying in sun too long - Tissue damage
- Lots of inflammatory cells floating around region of damage - pumping out bradykinin
- Binds to receptor on peripheral terminals of nociceptor
- Bradykinin receptor - metabotropic G coupled protein receptor
- Bradykinin binds to it - activates G protein - activates secondary messengers
- Activates protein kinases -> phosphorylate TRPV1 channel
- Reduces threshold - fires more easily
- That is peripheral sensitisation leading to primary hyperalgesia
51
Q
Mechanisms of action of bradykinin
- Bradykinin can alter sensitivity of the TRPV1 receptor
- Lying in sun too long - Tissue damage
- Lots of inflammatory cells floating around region of damage - pumping out bradykinin
- Binds to receptor on peripheral terminals of nociceptor
- Bradykinin receptor - … G coupled protein receptor
- Bradykinin binds to it - activates G protein - activates … messengers
- Activates protein … -> … TRPV1 channel
- … threshold - fires more …
- That is peripheral sensitisation leading to primary …
A
- Bradykinin can alter sensitivity of the TRPV1 receptor
- Lying in sun too long - Tissue damage
- Lots of inflammatory cells floating around region of damage - pumping out bradykinin
- Binds to receptor on peripheral terminals of nociceptor
- Bradykinin receptor - metabotropic G coupled protein receptor
- Bradykinin binds to it - activates G protein - activates secondary messengers
- Activates protein kinases -> phosphorylate TRPV1 channel
- Reduces threshold - fires more easily
- That is peripheral sensitisation leading to primary hyperalgesia
53
Q
Spinothalamic tract
- … information ascends the spinothalamic tract
- First order neuron (nociceptors):
- Cell body within … root ganglia
- Central terminus (central part of axon) is passing through the dorsal root to reach the dorsal …
- As central axon reaches the dorsal … of the spinal cord - forms collateral branches
- These either ascend or descend several spinal cord segments - they form a tract called the tract of …
- Within the tip of the dorsal horn - they synapse on the second order neuron
- Synapse in a region of the dorsal horn called the substantia …
- Grey matter spinal cord - divided into layers - substantia … - layer/lamina 1 and 2
- NT released from central terminals are … and substance … - both bind to second order neurons and excite them
A
- Pain information ascends the spinothalamic tract
- First order neuron (nociceptors):
- Cell body within dorsal root ganglia
- Central terminus (central part of axon) is passing through the dorsal root to reach the dorsal horn
- As central axon reaches the dorsal horn of the spinal cord - forms collateral branches
- These either ascend or descend several spinal cord segments - they form a tract called the tract of Lissauer
- Within the tip of the dorsal horn - they synapse on the second order neuron
- Synapse in a region of the dorsal horn called the substantia gelatinosa
- Grey matter spinal cord - divided into layers - substantia gelatinosa - layer/lamina 1 and 2
- NT released from central terminals are glutamate and substance P - both bind to second order neurons and excite them
54
Q
Spinothalamic tract
- … information ascends the spinothalamic tract
- First order neuron (…):
- Cell body within dorsal root ganglia
- Central terminus (central part of axon) is passing through the dorsal root to reach the dorsal horn
- As central axon reaches the dorsal horn of the spinal cord - forms … branches
- These either ascend or descend several spinal cord segments - they form a tract called the tract of Lissauer
- Within the tip of the dorsal horn - they synapse on the second order neuron
- Synapse in a region of the dorsal horn called the … gelatinosa
- Grey matter spinal cord - divided into layers - … gelatinosa - layer/lamina … and …
- NT released from central terminals are glutamate and substance P - both bind to second order neurons and excite them
A
- Pain information ascends the spinothalamic tract
- First order neuron (nociceptors):
- Cell body within dorsal root ganglia
- Central terminus (central part of axon) is passing through the dorsal root to reach the dorsal horn
- As central axon reaches the dorsal horn of the spinal cord - forms collateral branches
- These either ascend or descend several spinal cord segments - they form a tract called the tract of Lissauer
- Within the tip of the dorsal horn - they synapse on the second order neuron
- Synapse in a region of the dorsal horn called the substantia gelatinosa
- Grey matter spinal cord - divided into layers - substantia gelatinosa - layer/lamina 1 and 2
- NT released from central terminals are glutamate and substance P - both bind to second order neurons and excite them
55
Q
Second order neurons - Spinothalamic tract
- Second-order neurons:
- … in dorsal … at each level
- Ascend in … column to thalamus - within this - synapse on … order neurons
A
- Second-order neurons:
- Cross in dorsal horn at each level
- Ascend in anterolateral column to thalamus - within this - synapse on third order neurons
56
Q
Referred pain
- Convergence of visceral and cutaneous nociceptors on same … order neurons in the spinal cord
- Brain perceives … pain as…
- When pathway activated - brain doesn’t know whether the pain sensation is coming from the viscera or the skin - tends to be far more … nociceptors than … nociceptors - brain tends to perceive the pain as coming from the …
- Referred pain - MI - patients have angina - visceral nociceptors in the heart are activated - these activate second order neurons up towards your brain - synapsing on the same second-order neurons are lots of cutaneous nociceptors coming from the skin over the left arm
- When this is activated - brain thinks pain is coming from the skin over the left arm - where its perceived
A
- Convergence of visceral and cutaneous nociceptors on same second order neurons in the spinal cord
- Brain perceives visceral pain as cutaneous
- When pathway activated - brain doesn’t know whether the pain sensation is coming from the viscera or the skin - tends to be far more cutaneous nociceptors than visceral nociceptors - brain tends to perceive the pain as coming from the skin
- Referred pain - MI - patients have angina - visceral nociceptors in the heart are activated - these activate second order neurons up towards your brain - synapsing on the same second-order neurons are lots of cutaneous nociceptors coming from the skin over the left arm
- When this is activated - brain thinks pain is coming from the skin over the left arm - where its perceived
57
Q
Referred pain
- Convergence of visceral and cutaneous nociceptors on same second order neurons in the spinal cord
- Brain perceives visceral pain as cutaneous
- When pathway activated - brain doesn’t know whether the pain sensation is coming from the viscera or the skin - tends to be far more cutaneous nociceptors than visceral nociceptors - brain tends to perceive the pain as coming from the skin
- Referred pain - … - patients have angina - visceral nociceptors in the heart are activated - these activate second order neurons up towards your brain - synapsing on the same second-order neurons are lots of cutaneous nociceptors coming from the skin over the … arm
- When this is activated - brain thinks pain is coming from the skin over the … arm - where its …
A
- Convergence of visceral and cutaneous nociceptors on same second order neurons in the spinal cord
- Brain perceives visceral pain as cutaneous
- When pathway activated - brain doesn’t know whether the pain sensation is coming from the viscera or the skin - tends to be far more cutaneous nociceptors than visceral nociceptors - brain tends to perceive the pain as coming from the skin
- Referred pain - MI - patients have angina - visceral nociceptors in the heart are activated - these activate second order neurons up towards your brain - synapsing on the same second-order neurons are lots of cutaneous nociceptors coming from the skin over the left arm
- When this is activated - brain thinks pain is coming from the skin over the left arm - where its perceived
58
Q
Sensory component - Spinothalamic tract
- Third-order neurons: From thalamus - project all the way up towards the somatosensory cortex in the … lobe - synapse in the somatosensory cortex
- Ascend to primary somatosensory cortex
- Sensory … - lower body = medial, upper body = lateral
- Encode the sensory components
- Tells you “…” it hurts
- Modality - … of pain - …
A
- Third-order neurons: From thalamus - project all the way up towards the somatosensory cortex in the parietal lobe - synapse in the somatosensory cortex
- Ascend to primary somatosensory cortex
- Sensory homunculus - lower body = medial, upper body = lateral
- Encode the sensory components
- Tells you “where” it hurts
- Modality - type of pain - pressure, burn
- This is not pain
59
Q
Sensory component - Spinothalamic tract
- …-order neurons: From thalamus - project all the way up towards the … cortex in the parietal lobe - synapse in the … cortex
- Ascend to primary … cortex
- Sensory homunculus - … body = medial, … body = lateral
- Encode the sensory components
- Tells you “where” it hurts
- Modality - type of pain - pressure, burn
A
- Third-order neurons: From thalamus - project all the way up towards the somatosensory cortex in the parietal lobe - synapse in the somatosensory cortex
- Ascend to primary somatosensory cortex
- Sensory homunculus - lower body = medial, upper body = lateral
- Encode the sensory components
- Tells you “where” it hurts
- Modality - type of pain - pressure, burn
- This is not pain
60
Q
Emotional component - Spinothalamic tract
- Third-order neurons: Project to insula and … cortex
- Pain network -Many cortical regions activated (limbic system, prefrontal cortex)
- Encode the emotional components
- …
- … affect
- Activation of these regions make you … or … in pain, make you … because you’re in pain
- In patients who have lesions that affect the … - they can sense pain - they know when they’re injured, but it doesnt feel painful
A
- Third-order neurons: Project to insula and cingulate cortex
- Pain network -Many cortical regions activated (limbic system, prefrontal cortex)
- Encode the emotional components
- Unpleasantness
- Negative affect
- Activation of these regions make you scream or shout in pain, make you cry because you’re in pain
- In patients who have lesions that affect the insula - they can sense pain - they know when they’re injured, but it doesnt feel painful
61
Q
Emotional component - Spinothalamic tract
- Third-order neurons: Project to … and … cortex
- Pain network -Many cortical regions activated (… system, … cortex)
- Encode the emotional components
- Unpleasantness
- Negative affect
- Activation of these regions make you scream or shout in pain, make you cry because you’re in pain
- In patients who have … that affect the insula - they can sense pain - they know when they’re injured but it doesnt … painful
A
- Third-order neurons: Project to insula and cingulate cortex
- Pain network -Many cortical regions activated (limbic system, prefrontal cortex)
- Encode the emotional components
- Unpleasantness
- Negative affect
- Activation of these regions make you scream or shout in pain, make you cry because you’re in pain
- In patients who have lesions that affect the insula - they can sense pain - they know when they’re injured but it doesnt feel painful
62
Q
Pain experience
A
64
Q
Descending regulation of pain
- Two important regions
- … gray matter (PAG) - midbrain around cerebral … (first circle)
- … … medulla (RVM) - medulla (second circle)
- Cortical regions project to PAG
- PAG projects to RVM
- RVM projects to dorsal horn
- Modulates activity of spinothalamic tract
- Can be … and …
A
- Two important regions
- Periaqueductal gray matter (PAG) - midbrain around cerebral aqueducts (first circle)
- Rostral ventromedial medulla (RVM) - medulla (second circle)
- Cortical regions project to PAG
- PAG projects to RVM
- RVM projects to dorsal horn
- Modulates activity of spinothalamic tract
- Can be inhibitory and excitatory
65
Q
Descending regulation of pain
- Two important regions
- Periaqueductal … … (PAG) - midbrain around … aqueducts (first circle)
- Rostral ventromedial medulla (RVM) - medulla (second circle)
- … regions project to PAG
- PAG projects to RVM
- RVM projects to dorsal …
- Modulates activity of spinothalamic tract
- Can be inhibitory and excitatory
A
- Two important regions
- Periaqueductal gray matter (PAG) - midbrain around cerebral aqueducts (first circle)
- Rostral ventromedial medulla (RVM) - medulla (second circle)
- Cortical regions project to PAG
- PAG projects to RVM
- RVM projects to dorsal horn
- Modulates activity of spinothalamic tract
- Can be inhibitory and excitatory
66
Q
Inhibition of pain
- … grey matter neurons excite … neurons - cell bodies within RVM in medulla - axons of these project down towards dorsal horn, which excite inhibitory interneurons
- Inhibitory neurons - acting on our …-order neurons
- Inhibitory interneurons … spinothalamic tract neurons
- Parallel system that uses noradrenaline pathway rather than serotonin - via locus coeruleus
A
- Periaqueductal grey matter neurons excite serotonergic neurons - cell bodies within RVM in medulla - axons of these project down towards dorsal horn, which excite inhibitory interneurons
- Inhibitory neurons - acting on our second-order neurons
- Inhibitory interneurons inhibit spinothalamic tract neurons
- Parallel system that uses noradrenaline pathway rather than serotonin - via locus coeruleus
67
Q
Inhibition of pain
- Periaqueductal grey matter neurons excite serotonergic neurons - cell bodies within RVM in medulla - axons of these project down towards dorsal horn, which excite inhibitory …
- Inhibitory neurons - acting on our second-order neurons
- Inhibitory … inhibit spinothalamic tract neurons
- Parallel system that uses … pathway rather than serotonin - via locus …
A
- Periaqueductal grey matter neurons excite serotonergic neurons - cell bodies within RVM in medulla - axons of these project down towards dorsal horn, which excite inhibitory interneurons
- Inhibitory neurons - acting on our second-order neurons
- Inhibitory interneurons inhibit spinothalamic tract neurons
- Parallel system that uses noradrenaline pathway rather than serotonin - via locus coeruleus
