Pain 1 Flashcards

1
Q

What are examples of healthy pain and pathological pain?

A

healthy pain:

  • escape from danger
  • awareness of harm
  • treatment of tissue damage
  • learning about harmful environment

pathological pain:

  • migraine
  • neuropathic pain
  • back pain
  • joint pain (arthritis)
  • toothache
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2
Q

In general, what pathway does pain travel in?

A
  1. pain is detected by sensory receptors in the skin
  2. these travel via the somatic sensory neurones to the spinal cord
  3. neurones ascend through the medulla oblongata to the sensory cortex
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3
Q

Which part of the brain perceives pain?

A

the pain signal first goes to the thalamus

the thalamus sends the signal to a few different areas for interpretations

it also sends signals to the limbic system, which is the emotional centre of the brain

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4
Q

What are the 5 different sensory receptors in the skin?

A
  1. Meissner corpuscle
  2. Pacinian corpuscle
  3. Ruffini’s corpuscle
  4. Merkel’s disks
  5. free nerve endings
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5
Q

Which sensory receptors are found just beneath the epidermis?

A

Meissner corpuscles and Merkel’s disks

Meissners corpuscles sit between the dermal pupillae

Merkel’s disks are aligned with the dermal pupillae

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6
Q

Where are pacinian corpuscles located?

A

they are large encapsulated endings located in the subcutaneous tissue

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7
Q

Where are Ruffini’s corpuscles located?

A

they are located deep in the dermis

the long axis of the corpuscle is orientated parallel to the skin

they form 20% of receptors in the skin

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8
Q

How is conduction velocity associated with axon diameter?

A

conduction velocity is positively correlated with axon diameter

(larger diameter axons have faster conduction velocity)

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9
Q

What types of axons of sensory afferents innervating somatosensory receptors have a large diameter?

A

large diameter, rapidly conducting afferents (I / II) are associated with low threshold mechanoreceptors

e.g. proprioceptors of skeletal muscle, mechnoreceptors of skin

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10
Q

what types of axons of sensory afferents innervating somatosensory receptors have a small diameter?

A

small diameter, slow conducting afferents (III / IV) are associated with nociceptors and thermoreceptors

both type III and IV fibres are involved in conducting pain sensation

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11
Q

What are the two categories of pain perception?

Which fibres do they travel in?

A

different fibres convey different aspects of pain sensation

first pain:

  • conveyed through fast Ad fibres

second pain:

  • conveyed through slow C-fibres
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12
Q

What is the difference in sensation between first and second pain?

A

a single painful stimulus yields two successive and distinct sensations

first pain:

  • brief, pricking and well localised

second pain:

  • longer-lasting, burning and less well localised
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13
Q

What are the characteristics of first pain?

What types of receptors produce this kind of pain?

What is the duration like?

A

conducted via fast Ad fibres

  • sharp or prickling
  • easily localised
  • occurs rapidly
  • short duration

mechanical or thermal nociceptors

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14
Q

What are the characteristics of second pain?

What types of receptors detect this pain?

A

carried by slow C-fibres

  • dull ache, burning
  • poorly localised
  • slow onset
  • persistent

sensory receptors are polymodal nociceptors

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15
Q

What are the spinal connections of the nociceptive axon terminals?

A
  • afferent terminals enter the dorsal horn and project into the zone of lissauer
  • afferent terminals synapse onto neurones of lamina I and lamina II (substantia gelatinosa)
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16
Q

What are the connections between the primary afferent pain fibres and the spinal cord?

A

AB myelinated fibres:

  • synapse with PKCy+ neurones and lamina V

Peptidergic C fibres:

  • synapse with lamina I

Ad myelinated fibres:

  • synapse with outer lamina II and lamina V

nonpeptidergic C fibres:

  • synapse with inner lamina II
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17
Q

What are the 3 different neurones involved in the spinal pain pathway?

A

first order neurones:

  • pseudounipolar neurones have a cell body in the DRG

second order neurones:

  • cell body in Rexed lamina of spinal cord or cranial nerve nuclei in the brainstem
  • decussate in anterior white commisure
  • ascend cranially in the spinothalamic tract to the VPL of the thalamus

third order neurone:

  • cell body in the VPL of the thalamus
  • project via posterior limb of internal capsule to terminate in ipsilateral postcentral gyrus
  • this is the primary somatosensory cortex
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18
Q

What are the specialised receptors that some first order neurones have?

What type of receptors are these?

A

nociceptors which are activated through various noxious stimuli

nociceptors exist as the free nerve endings of the primary afferent neurone

as they are free nerve endings, they are unencapsulated receptors

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19
Q

What are the 3 different types of nociceptors?

What type of stimulus do they detect?

A

mechanical nociceptors:

  • detect sharp, prickling pain

thermal / mechano-thermal nociceptors:

  • detect sensations which elicit pain which is slow and burning or cold and sharp in nature

polymodal nociceptors:

  • detect mechanical, chemical and thermal stimuli
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20
Q

How are signals from mechanical, thermal and mechano-thermal nociceptors transmitted?

A

they are transmitted to the dorsal horn via Ad fibres

these are myelinated and have a low threshold for firing and fast conduction speed

they are responsible for transmitting the first pain

they permit localisation of pain

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21
Q

Where do Ad fibres terminate?

A

rexed lamina I

they mainly release the neurotransmitter glutamate

22
Q

How do polymodal nociceptors transmit their signals to the dorsal horn?

A

via C-fibres

these are unmyelinated and have a slow conduction speed

they have large receptive fields and poor localisation of pain

23
Q

Where do C fibres terminate?

A

in rexed laminae I and II

they release the neurotransmitter substance P

24
Q

What are the roles of the cingulate cortex and insular cortex in pain perception?

A

cingulate cortex:

  • acute pain perception
  • development of chronic pain after peripheral nerve injury

insular cortex:

  • part of the limbic system
  • subjective feeling of pain and induce learning about the pain in other brain areas
25
What is meant by 'dissociated sensory loss'?
a pattern of neurological damage caused by a lesion to a single tract in the spinal cord it involves preservation of fine touch and proprioception and selective loss of pain and temperature
26
In a unilateral spinal lesion, how would senses be affected?
* sensory loss of **touch, pressure, vibration** and **proprioception** **_BELOW**_ the lesion on the _**SAME_** side * diminished sensation of pain **_BELOW_** the lesion on the **_OPPOSITE_** side * this is dissociated sensory loss
27
What are the 3 neurones involved in the trigeminal pathway for pain and temperature?
**1st order neurone:** * from the face * projects to pars interpolaris & pars caudalis of the medulla / upper cervical cord **2nd order neurone:** * ascends contralaterally to thalamus via trigeminothalamic tract **3rd order neurone:** * projects to cortex from VPM of thalamus this pathway innervates speicialised structures
28
What is meant by the gate control theory of pain?
a gating mechanism that exists within the **dorsal horn** of the spinal cord small nerve fibres (pain receptors) and large nerve firbes (mechanoreceptors) synpase on **projection cells** and **inhibitory interneurones** projection neurones travel to the brain via the spinothalamic tract
29
According to gate control theory, what happens when no input comes in?
the inhibitory interneurone prevents the projection neurone from sending signals to the thalamus the gate is closed
30
According to gate control theory, what happens when there is normal somatosensory input? (more / only large fibre stimulation)
both the inhibitory interneurone and projection neurone are stimulated the inhibitory interneurone prevents the projection neurone from sending signals to the brain the gate is closed
31
According to gate control theory, what happens when there is more/only small fibre stimulation? (nociception)
the inhibitory interneurone is inactivated the projection neurone sends signals to the thalamus informing it of pain the gate is open
32
According to gate control theory, what is the role of the descending pathways from the brain?
descending pathways from the brain close the gate by inhibiting the projector neurones and dimishing pain perception
33
What are the 2 different types of pain?
**physiological pain:** * this involves acute pain **pathological pain:** * this involves inflammatory and chronic pain
34
What is the primary event in somatosensation?
the generation of an action potential in an afferent fibre ending
35
What regulators of neuronal excitability are specific for nociceptive neurones?
**voltage-gated sodium channels:** * Nav1.7 * Nav1.8 * Nav1.9 **sensory TRP channels:** * TRPV1 * TRPM8 * TRPA1 **purinergic ligand-gated channels:** * P2X2 * P2X3
36
What is meant by congenital insensitivity to pain?
a rare disease characterised by inability of experience to feel pain
37
What tends to cause congenital insensitivity to pain?
mutations within nociceptor-specific voltage-gated sodium channel Nav1.7 population genetics can be used to pin-point pain-related genes
38
What are the 4 different types of inflammatory mediators of pain?
1. act to directly activate ligand-gated ion channels 2. act via activation of G-protein coupled receptors 3. act via activation of receptor tyrosine kinases 4. gasotransmitters
39
What types of inflammatory mediators act to directly activate ligand-gated ion channels?
* ATP activates P2X receptors * H+ activates TRPV1
40
What inflammatory mediators act via activation of G-protein coupled receptors?
* prostaglandins * substance P * bradykinin * proteases * histamine
41
What inflammatory mediators act via activation of receptor tyrosine kinases?
* NGF * BDNF
42
What are examples of gasotransmitters?
these are gaseous signalling molecules * CO * NO * H2S
43
What are the 3 mechanisms involved in signalling cascades of inflammatory nociception?
1. activation / sensitisation of sensory channels 2. modulation of ion channels through intracellular signalling cascades 3. modulation of gene expression
44
What is the role of central sensitisation?
central sensitisation contributes to **sustained pain states** it is a condition of the nervous system that is associated with the **development & maintenance of chronic pain** when it occurs, the nervous system goes through the process of **wind-up** and gets regulated in a persistent state of high reactivity
45
What is the definition of central sensitisation?
the process through which a state of hyperexcitability is established in the central nervous system this leads to enhanced processing of nociceptive (pain) messages
46
What are the 3 main mechanisms of central sensitisation?
1. NMDA-mediated signalling 2. disinhibition 3. microglia activation
47
What is familial hemiplegic migraine (FHM)?
an autosomal dominant subtype of severe migraine accompanied by visual disturbances known as aura
48
What causes the aura in familial hemiplegic migraine?
aura is caused by cortical spreading depression (CSD) this is a slowly advancing wave of tissue depolarisation in the cortex
49
What is the cause of more than half of the cases of familial hemiplegic migraine?
gain-of-function mutations within neuronal Cav2.1 voltage-gated Ca2+ channel gene the mutation results in increased Ca2+ flow into dendrites and excessive release of the excitatory neurotransmitter glutamate
50
What initiates cortical spreading depression (CSD)?
CSD is ignited by local elevation of **extracellular K+ levels** in pockets of intense excitatory transmission
51
How is CSD threshold altered in FHM patients?
the threshold for CSD initiation is reduced in FHM patients with mutations in the Cav2.1 Ca2+ channel the higher Ca2+ level in dendrites facilitates glutamate release this increases the likelihood that K+ levels will reach the CSD threshold
52