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Physiology of Pain Flashcards

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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
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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
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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

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4
Q

What are the sensations of pain?

A
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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
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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
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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
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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
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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
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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
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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
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12
Q

which afferent nerve fibre recognise pain?

A
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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

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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
  • 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
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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
  • 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
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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
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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
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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.

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19
Q

… … fibers carry sharp/pricking pain

A

A deltafibers carry sharp/pricking pain

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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
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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
  • 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
  • Visceral pain - no first response - innervated by C-fibres, not a-delta fibres
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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
  • … 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
  • Visceral pain - no first response - innervated by C-fibres, not a-delta fibres
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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

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24
Q

Activation of nociceptors:

  • P…
  • Heat
  • C…
  • C…
  • Tissue …/…
A
  • Pressure
  • Heat
  • Cold
  • Chemical
  • Tissue damage/inflammation
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25
* Most c-fibre nociceptors are polymodal - respond to: * Respond to ..., ... and ...
* Most c-fibre nociceptors are polymodal - respond to: * Respond to pressure, temperature and chemical
26
_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?
* 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
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 ... ... ....
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
_Pressure transduction_ * ... sensitive ... channels respond to pressure * Precise ... not yet identified (possibly acid sensing ion channels, transient receptor potential channels)
* Mechanically sensitive ion channels respond to pressure * Precise channels not yet identified (possibly acid sensing ion channels, transient receptor potential channels)
29
_Temperature transduction_ * ... ... potential ... of channels transduce different temperatures - large group of channels that detect different temperatures
* **Transient receptor potential family** of channels transduce different temperatures - large group of channels that detect different temperatures * Detect different temperatures
30
_Temperature transduction_ * Transient receptor potential family of channels transduce different temperatures - large group of channels that detect different temperatures * Detect different temperatures
* Transient receptor potential family of channels transduce different temperatures - large group of channels that detect different temperatures * Detect different temperatures
31
TRPV1 - temp is ... - agonist is ...
32
TRPM - temp is ... - agonist is ...
33
TRPA1 - temp is ... - agonist is ...
34
_Inflammation and tissue injury_ Chemicals released as part of tissue injury and inflammation have ... effects on ...
* Chemicals released as part of tissue injury and inflammation have excitatory effects on nociceptors
35
_Activation of nociceptors by inflammation_ * For example, ..., protons and ... can activate nociceptors
* For example, ATP, protons and serotonin can activate nociceptors
36
_Activation of nociceptors by inflammation_ * ... - binds to purinergic receptors or P2X receptors sitting on the peripheral terminal of your nociceptors * ... - bind to acid sensing ion channels and switch on the nociceptor * ... - bind to 5-HT receptors - sitting at terminals of nociceptors
* ATP - binds to purinergic receptors or P2X receptors sitting on the peripheral terminal of your nociceptors * Protons - bind to acid sensing ion channels and switch on the nociceptor * Serotonin - bind to 5-HT receptors - sitting at terminals of nociceptors
37
_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
* 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
_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
* 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
_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
* 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
_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
* 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
41
* ... - Non-noxious stimuli produce a painful response * No pain perceived as painful - ... pain patients - light brushing = PAIN
* Allodynia - Non-noxious stimuli produce a painful response * No pain perceived as painful - neuropathic pain patients - light brushing = painful
42
* ... - Noxious stimuli produce an exaggerated pain response * Pain is worse
* Hyperalgesia - Noxious stimuli produce an exaggerated pain response * Pain is worse
43
_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 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
44
_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
* 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
45
Central sensitization is a major mechanism in ... pain
Central sensitization is a major mechanism in **neuropathic** pain
46
_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
* 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
_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
* 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
48
Sunburn - example of causing ... sensitization
**Sunburn - example of causing peripheral sensitization**
49
* ... - example of causing peripheral sensitization * Warm shower feels painful to ...
* Sunburn - example of causing peripheral sensitization * Warm shower feels painful to burns
50
_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
* 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
_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 ...
* 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
52
Bradykinin can alter sensitivity of the ... receptor
## Footnote **Bradykinin can alter sensitivity of the TRPV1 receptor**
53
_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
* 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
_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
* 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
_Second order neurons - Spinothalamic tract_ * Second-order neurons: * ... in dorsal ... at each level * Ascend in ... column to thalamus - within this - synapse on ... order neurons
* Second-order neurons: * Cross in dorsal horn at each level * Ascend in anterolateral column to thalamus - within this - synapse on third order neurons
56
_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
* 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
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_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 ...
* 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
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_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 - ...
* 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
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_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
* 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
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_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
* 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
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_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
* 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
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Pain experience
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_Stress induced analgesia_ * For survival it may be necessary to ... pain * Called stress-induced analgesia * E.g. - Battle victims * ... athletes (swimming, running etc) * Higher cortical regions can activate ... ... pathways
* For survival it may be necessary to supress pain * Called stress-induced analgesia * E.g. - Battle victims * Endurance athletes (swimming, running etc) * Higher cortical regions can activate descending modulatory pathways
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_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 ...
* 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
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_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
* 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
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_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
* 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
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_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 ...
* 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
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_Endogenous opioid system_ * Opioids play an important role in the ... of pain (E.g. Endorphins, enkephalins) * Opioids are inhibitory - Act on inhibitory ... receptors (G protein coupled receptors - that activate secondary messengers) * Released from interneurons at multiple sites throughout CNS (they're found within the ... grey matter, RVM and dorsal horn) * Inhibitory interneurons in the dorsal horn would directly inhibit the secondary order ... tract neurons as shown previously
* Opioids play an important role in the **inhibition** of pain (E.g. Endorphins, enkephalins) * Opioids are inhibitory - Act on inhibitory **metabotropic** receptors (G protein coupled receptors - that activate secondary messengers) * Released from interneurons at multiple sites throughout CNS (they're found within the **periaqueductal** grey matter, RVM and dorsal horn) * Inhibitory interneurons in the dorsal horn would directly inhibit the secondary order spinothalamic tract neurons as shown previously
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_Endogenous opioid system_ * Opioids play an important role in the inhibition of pain (E.g. Endorphins, enkephalins) * Opioids are inhibitory - Act on inhibitory metabotropic receptors (... protein coupled receptors - that activate ... messengers) * Released from interneurons at multiple sites throughout CNS (they're found within the periaqueductal grey matter, ... and ... horn) * Inhibitory interneurons in the dorsal horn would directly inhibit the secondary order spinothalamic tract neurons as shown previously
* Opioids play an important role in the inhibition of pain (E.g. Endorphins, enkephalins) * Opioids are inhibitory - Act on inhibitory metabotropic receptors (G protein coupled receptors - that activate secondary messengers) * Released from interneurons at multiple sites throughout CNS (they're found within the periaqueductal grey matter, RVM and dorsal horn) * Inhibitory interneurons in the dorsal horn would directly inhibit the secondary order spinothalamic tract neurons as shown previously
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* RVM - opioids inhibit inhibitory interneurons - disinhibition * Would otherwise switch off those descending serotonergic projections down towards the dorsal horn * Consequence - ... of this descending pathway
* RVM - opioids inhibit inhibitory interneurons - disinhibition * Would otherwise switch off those descending serotonergic projections down towards the dorsal horn * Consequence - activation of this descending pathway

Year 2 Medicine (162 decks)

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