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Revision K - Pain Science > Pain physiology > Flashcards

Pain physiology Flashcards

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1
Q

What are the 4 types of nociceptors?

A

Thermal

  • activated by heat or cold
  • A delta fibres

Mechanical

  • activated by high pressure
  • A delta fibres

Polymodal

  • activated by mechanical, thermal and/or chemical (pH, bradykinin and histamines)
  • C fibres

Silent:
- normally inactive but can become activated in response to noxious stimuli released by tissue injury

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2
Q

What are the 2 types of neurons that convey nociceptive signals, and what type of pain do they generate?

A

A delta

  • fast pain
  • temperature (heat)

C

  • slow pain
  • temperature (cold)
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3
Q

What are the 3 substances that can activate peripheral nociceptors?

A

Potassium (from damaged cells)
Serotonin (from platelets)
Bradykinin (from plasma)
Histamine (from mast cells)

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4
Q

What are the 3 substances that can sensitize peripheral nociceptors?

A

Prostaglandins (from damaged cells)
Leukotrienes (from damaged cells)
Substance P (neuropeptide from damaged nerves)

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5
Q

What are the 7 chemicals that create an inflammatory soup and activate and sensitize peripheral nociceptors?

A

Activate:

  • potassium
  • serotonin
  • bradykinins
  • histamine

Sensitize:

  • prostaglandins
  • leukotrienes
  • substance P
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6
Q

What are the 4 effects of inflammatory chemical soup on peripheral nociceptors?

A
  • lower threshold for AP generation
  • potential for ectopic AP generation
  • increased receptive field size
  • recruitment of silent nociceptors
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7
Q

What are the 4 steps in the nociceptive pathway?

A
  1. transduction (generation of an AP in a primary afferent nociceptor / PAN)
  2. transmission (transmission of nociceptive signal from 1st order to 2nd order neuron in the dorsal horn of the spinal cord; from the 2nd order neuron to the 3rd order neuron in the VPN of the thalamus; and termination of the 3rd order neuron in the primary somatosensory cortex)
  3. modulation (occurs in dorsal horn; includes descending inhibitory pathways, presence of excitatory or inhibitory subtances, and interaction between incoming signals ie: gate control theory)
  4. perception (thalamus and sensory cortex - sensory discriminative; reticular formation and limbic system - motivational affective; hypothalamus - ANS response)
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8
Q

What are the 3 types of neurons involved in transmission and modulation in the dorsal horn?

A

Interneurons:
- can be excitatory or inhibitory

Wide Dynamic Neurons:
- receive input from both noxious and non-noxious neurons via interneurons

Projection cells:
- project to brain

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9
Q

What are the 4 types of neurons transmitting signals to the dorsal horn of the spinal cord, and what type of information do they convey?

A

Noxious:

  • A delta (fast pain, heat)
  • C (slow pain, viscera, cold)

Non-noxious:

  • A alpha (somatic mm, propioception)
  • A beta (touch, vibration, pressure)
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10
Q

Describe the 5 steps in the spinothalamic pathway

A
  1. 1st order neuron (PAN) transmits AP from periphery to dorsal horn of spinal cord
  2. modulation of signal in dorsal horn (via interneurons, gate theory, descending inhibitory pathways, presence of excitatory or inhibitory substances)
  3. synapse between 1st and 2nd order neurons in dorsal horn via interneurons and/or wide dynamic neurons
  4. 2nd order neuron decussates at spinal cord and ascends to VPN in thalamus; synapses with 3rd order neuron
  5. 3rd order neuron terminates in primary somatosensory cortex
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11
Q

What are transient receptor potential channels?

A

TRP channels:

  • respond to a number of strong stimuli
  • also involved in transmission of burning sensation of chilli
  • capasin can be used as an analgesic by targeting TRP channels
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12
Q

Which neurons in the dorsal horn of the spinal cord may be responsible for referred pain?

A

Wide dynamic neurons:

  • receive input from both noxious and non-noxious pathways via interneurons
  • may be responsible for referred pain via misinterpretation of incoming stimuli
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13
Q

What are the 2 primary pathways that transmit noxious signals?

A

Spinothalamic (from body)

Trigeminal (from face)

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14
Q

What are the 2 neuropeptides?

A

Substance P
CGRP (calcitonin gene-related peptide)

  • released by PANs, can play a role in peripheral sensitization
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15
Q

What are the 3 major areas of the brain that play a role in pain perception, and which elements of the pain experience do they contribute to?

A
  1. Thalamus and somatosensory cortex - sensory discriminative aspect
  2. Anterior insular, cingulate cortices, reticular system and limbic system - motivational affective aspect
  3. Hypothalamus - ANS response
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16
Q

In the dorsal horn, which 2 receptors facilitate the transmission of nociceptive signals; and which 2 receptors inhibit the transmission of nociceptive signals?

A

Facilitate:

  • substance P
  • glutamate (NMDA and non-NMDA - AMPA and GABA)

Inhibit:

  • serotonin
  • norepinephrine
17
Q

In the dorsal horn, which 2 receptors facilitate the transmission of nociceptive signals; and which substances can be used to inhibit these receptors and therefore inhibit the transmission of nociceptive signals?

A

Facilitate:

  • substance P
  • glutamate (NMDA and non-NMDA - AMPA and GABA)

Substances inhibiting these receptors:

  • ketamine (NMDA receptors)
  • baclofen (GABA receptors)

Other inhibitory substances:

  • calcitonin
  • octreotide (somatostatin receptors)
  • clonidine (alpha 2 receptors)
18
Q

What are NMDA receptors?

A
  • receptors in dorsal horn
  • normally inactive
  • become activated by a barrage of APs releasing chemicals into the dorsal horn
  • facilitate transmission of nociceptive signals at dorsal horn
  • involved in neuropathic pain and central (secondary) hyperalgesia
  • inhibited by ketamine
19
Q

Which substances are released by the descending inhibitory pathway, and what are their actions?

A

Seratonin and norepinephrine
- directly released by neuron descending from PAG via RVM

Endogenous opioids:
- release from interneurons in the dorsal horn (release triggered by serotonin and norepinephrine from the descending inhibitory neuron)

Actions:

  • inhibits release of substance P and AP from 1st order neuron
  • hyperpolarizes 2nd order neuron and makes generation of a nociceptive AP less likely
20
Q

Describe the descending inhibitory pathway

A
  1. originates in PAG
  2. neuron travels to RVM and lateral pontine tegmentum and synapses with 2nd neuron
  3. 2nd neuron descends to dorsal horn of spinal cord; releases norepinephrine and serotonin and causes the release of endogenous opioids from interneurons in the dorsal horn

Actions:

  • inhibits release of substance P and transmission of AP from 1st order neuron (PAN)
  • hyperpolarizes 2nd order neuron to make generation of an AP less likely
21
Q

Briefly describe the 4 steps involved in the generation of an action potential.

A
  1. membrane of neuron resting at 70mv
  2. sodium or calcium enters membrane via voltage gated channels, depolarizing membrane
  3. action potential generated at 40mv
  4. membrane of neuron repolarizes by closing calcium or sodium channels, and opening potassium channels
22
Q

Briefly describe the 6 steps involved in synaptic transmission of an action potential

A
  1. AP arrives at the pre-synaptic axon terminal
  2. AP opens calcium gated channels on axon terminal membrane
  3. calcium triggers release of neurotransmitter from pre-synaptic neuron into synaptic cleft
  4. neurotransmitter travels across synaptic cleft and binds to receptors on post-synaptic neuron
  5. neurotransmitter triggers opening of sodium or calcium channels on post-synaptic neuron
  6. post-synaptic neuron depolarizes, AP generated at 40mv
23
Q

What is the difference between the PAG, the RVM, and the VPL?

A

PAG:

  • periacqueductal gray
  • area of the brain that initiates descending inhibitory pathways

RVM:

  • rostral ventral medulla
  • synapse between 1st and 2nd neurons in descending inhibitory pathway

VPL:

  • ventral posterolateral nucleus in thalamus
  • site of synapse between 2nd and 3rd order neurons in ascending spinothalamic tract
24
Q

Describe the points of synapse between neurons in the spinothalamic tract

A
  1. 1st and 2nd order neurons synapse in the dorsal horn of the spinal cord
  2. 2nd and 3rd order neurons synapse in the VPL (ventral posterolateral nucleus) in the thalamus
  3. 3rd order neuron terminates in the primary somatosensory cortex of the parietal lobe
25
Q

Where are the cell bodies of peripheral afferent neurons?

A

In the dorsal root ganglia (with one projection to the periphery and another projection to the dorsal horn)

Revision K - Pain Science (5 decks)

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