Physiology of Pain Flashcards

1
Q

Pain is classified by what three forms?

A
  • Nociceptive pain: maladaptive.
  • Inflammatory pain: adaptive.
  • Pathological pain: maladaptive.
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2
Q

Describe nociceptive pain.

A
  • Adaptive.
  • Immediate protective response.
  • Short-lived.
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3
Q

Describe inflammatory pain.

A
  • Adaptive.
  • Assists in healing.
  • Persists over days, possibly weeks.
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4
Q

Describe pathological pain.

A
  • Maladaptive.
  • No physiological purpose.
  • Persists over months, years or even a lifetime.
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5
Q

Acute mild pain is often controlled effectively by what?

A
  • NSAIDs +/- paracetamol.
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6
Q

Moderate severe cases of pain may require addition of what to NSAIDs/paracetamol?

A

Opioids

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7
Q

Chronic pain may sometimes be managed by alternative drug classes such as?

A
  • Anti-depressants.
  • Anti-convulsants.
  • Local anaesthetics.
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8
Q

How may pain in skin present?

A
  • Well localised.

- Pricking, stabbing, burning.

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9
Q

How may pain of muscle present?

A
  • Poorly localised.

- Aching, soreness/tenderness, cramping/stabbing/burning.

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10
Q

How may pain of viscera present?

A
  • Poorly localised (often referred to a somatic structure).

- Dull, vague, fullness, nausea.

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11
Q

What are nociceptors?

A

Specific peripheral primary sensory afferent neurones.

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12
Q

What normally activates nociceptors?

A

Preferentially activated by intense noxious stimuli e.g. thermal, mechanical, chemical.

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13
Q

Describe the relay of nociceptors to the CNS.

A
  • Nociceptors are 1st order neurons relaying information by APs to 2nd order neurons of CNS by chemical synaptic transmission.
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14
Q

Nociceptors innervate what?

A

They are primary afferent neurons innervating peripheral tissues.

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15
Q

Nociceptors are comprised of what type of fibres?

A
  • Aδ- and C-fibres.

NB not all of these fibres are nociceptors.

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16
Q

Aδ-fibres are what kind of nociceptors?

A

Mechanical/thermal nociceptors that are thinly myelinated

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17
Q

Aδ-fibres contribute to nociceptors that respond to what?

A

Noxious mechanical and thermal stimuli.

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18
Q

Aδ-fibres mediate what kind of pain?

A
  • First or fast pain.
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19
Q

C-fibres are what kind of nociceptors?

A

Unmyelinated.

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20
Q

C-fibres contribute to nociceptors that respond to what?

A

ALL noxious stimuli - they are polymodal.

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21
Q

C-fibre nociceptors mediate what kind of pain?

A

“second”/slow pain.

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22
Q

Describe “first”/fast pain of Aδ-fibre nociceptors.

A
  • Lancinating, stabbing, pricking.
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23
Q

Describe “second”/slow pain of C-fibre nociceptors.

A
  • Burning, throbbing, cramping, aching sensations.
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24
Q

Noxious thermal stimuli activate which receptors?

A

Members of the transient receptor potential (TRP).

- Especially TRPA1, TRPC3, TRPV1.

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25
Q

Which member of the transient receptor potential (TRP) family is greatly sensitised in inflammation to become active at body temperature?

A

TRPV1.

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26
Q

Chemical stimuli activates what?

A
  • H+: Acid sensing ion channels (ASICs).
  • ATP: P2X and P2Y receptors.
  • Bradykinin: B2 receptors.
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27
Q

Where do the axons of nociceptor (1st order) synapse with 2nd order neurons?

A

Dorsal (posterior) horn of spinal cord.

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28
Q

The afferent branch of peptidergic polymodal nociceptors have which function?

A

To transmit nociceptive info to CNS via release of glutamate and peptides within the dorsal horn.

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29
Q

The efferent branch of peptidergic polymodal nociceptors have which function?

A

Release pro-inflammatory mediators e.g. CGRP from peripheral terminals (contributes to neurogenic inflammation).

30
Q

Long term noxious stimulation increases what?

A

Spinal excitability, contributing to hyperalgesia and allodynia.

31
Q

In neurogenic inflammation, peptides (SP & CGRP) are released from free nerve endings of peptidergic nociceptors due to what?

A

Tissue damage or inflammatory mediators.

32
Q

The peptide SP causes what?

A
  • Vasodilation and extravasation of plasma proteins (promotes formation of bradykinin and prostaglandins).
  • Histamine release from mast cells.
  • Sensitisation of surrounding nociceptors.
33
Q

The peptide CGRP induces what?

A

Vasodilation.

34
Q

What ultimately results from release of SP and CGRP in neurogenic inflammation?

A

Primary and secondary hyperalgesia and allodynia.

35
Q

Primary afferent cell bodies are located in the dorsal root ganglia, apart from which system?

A

The trigeminal system.

36
Q

In the neurotransmission between the primary afferent and second order neuron in dorsal horn, what is the primary transmitter?

A

Glutamate.

- Produces fast e.p.sp. and neuronal excitation.

37
Q

In the neurotransmission between the primary afferent and second order neuron in dorsal horn, Glutamate produces a fast e.p.s.p. and neuronal excitation by doing what?

A

Activating primarily postsynaptic AMPA receptors with NMDA receptor participation.

38
Q

What peptides - except glutamate - also participate in the neurotransmission between the primary afferent and second order neuron in dorsal horn?

A

Substance P and CGRP, particularly during high frequency stimulation.

39
Q

Substance P and CGRP in the neurotransmission between the primary afferent and second order neuron in dorsal horn cause what?

A

Slow and prolonged e.p.s.p. that facilitates activation of NMDA receptors, by relieving voltage-dependent block by Mg2+.

40
Q

Where do most nociceptive C- and Aδ-fibre nociceptors terminate superficially?

A

In laminae I and II of the laminae of Rexed.

  • Also V for Aδ-fibres.
41
Q

Nociceptive specific (NS) cells, synapse only with what?

A

C- and Aδ-fibres.

42
Q

The central projections of primary afferent axon fibres terminate where>

A

Dorsal horn of the spinal cord in various laminae of Rexed.

43
Q

Cells that receive input from only Aβ-fibres are what?

A

Proprioceptive.

44
Q

Wide dynamic range (WDR) neurons receive input from what types of fibres?

A
  • C-fibres.
  • Aβ-fibres.
  • Aδ-fibres.
45
Q
WDR neurons receive input from:
 - C-fibres.
- Aβ-fibres.
- Aδ-fibres.
Meaning what?
A

They respond to a wide range of stimuli.

46
Q

Visceral pain originates from what structures?

A

Nociceptors covering tissues (e.g. peritoneum, pleura) or the walls of hollow organs.

47
Q

Visceral pain originates from what (not structures)?

A
  • Stretching, twisting, inflammation and ischaemia.

But NOT cutting or burning.

48
Q

Visceral pain tends to be described as?

A

Poorly localised, dull, aching, throbbing.

49
Q

Visceral afferents from nociceptors follow what pathways before entering the dorsal horn?

A

Sympathetic.

50
Q

Some visceral and skin afferents converved upon what neurons?

A

Spinothalamic.

51
Q

Terminals of visceral nociceptors terminate in which laminae?

A

I and V.

NOT II.

52
Q

What gives rise to referred pain?

A

Brain interprets nociceptive information from viscera as arising from an area of skin (may be distant to internal organ).

53
Q

Visceral referred pain is often associated with which autonomic features?

A

Nausea, vomiting, sweating, pallor etc.

54
Q

Area of visceral pain referral is to where?

A

The segmental dermatome which may show signs of hyperalgesia.
- e.g. heart T1-5, gallbladder C4.

55
Q

Viscerosomatic pain is described as?

A

Sharp and well localised.

56
Q

When does viscerosomatic pain occur?

A

When inflammatory exudate from a diseased organ contacts a somatic structure.

57
Q

Pain evoked by activity in:
- C-fibres.
- Aδ-fibres.
may be reduced by simultaneous activity in what?

A

Low threshold mechanoreceptors i.e. Aβ-fibres.

58
Q

Projection (P) neurones within substantial gelatinosa project to the spinothalamic tract and thought to be excited by what?

A
  • Large diameter (Aβ) sensory axons.

- Unmyelinated (C/Aδ) nociceptive axons.

59
Q

Projection neuron inputs are inhibited by what?

A

An interneuron.

60
Q

What excites the interneuron inhibiting projection neuron inputs?

A
  • Large diameter (Aβ) sensory axons.
61
Q

What inhibits the interneuron inhibiting projection neuron inputs?

A
  • Unmyelinated (C/Aδ) nociceptive axons.
62
Q

Maximal excitation of the projection neuron is due to what?

A

Activity solely in the unmyelinated (C/Aδ) nociceptive axons.

63
Q

Maximal excitation of the projection neuron allows what?

A

Nociceptive signals to arise to the brain.

64
Q

Second order neurones (of major nociceptive tracts) ascend the spinal cord in the anterolateral system, comprising mainly of what tracts?

A
  • Spinothalamic tract.

- Spinoreticular tract.

65
Q

Projection neurons of the spinothalamic tract originate from where?

A

Lamina I.

Lamina V.

66
Q

Where do projection neurons of the spinothalamic tract originating from lamina I terminate?

A

Posterior nucleus of thalamus.

67
Q

Where do projection neurons of the spinothalamic tract originating from lamina V (WDR) terminate?

A

Posterior and ventroposterior nucleus of thalamus.

68
Q

The spinoreticular tract largely transmits what type of pain?

A

Slow C-fibre pain.

69
Q

The spinoreticular tract makes extensive connections with what in the brainstem?

A

Reticular nuclei e.g. periaqueductal grey and parabrachial nucleus.

70
Q

The spinoreticular tract is involved in autonomic responses to what?

A

Pain, arousal, emotional responses, fear of pain.

71
Q

Thermoreceptors are neurons specialised to respond to what?

A

Small changes in temperature.

72
Q

Why is temperature sensitivity not uniform across the body surface?

A
  • Hot-sensitive and cold-sensitive spots exist.