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Neuro 3 > Lecture 18: Pain (peripheral nervous system pain) > Flashcards

Lecture 18: Pain (peripheral nervous system pain) Flashcards

1
Q

What is conduction velocity in an axon enhanced by?

A

Myelination

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2
Q

What does myelination do?

A

Enhances conduction velocity in an axon

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3
Q

What are axons in the CNS mylinated by?

A

Oligodendrocytes

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4
Q

What do oligodendrocytes mylinate?

A

Axons in the CNS

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5
Q

What myelinates axons in the PNS?

A

Schwann cells

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6
Q

What do Schwann cells do?

A

Myelinate axons in the PNS

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7
Q

What happens during the myelination process?

A

An axon is ensheathed by a glial cell which extrudes its cytoplasm. The cytoplasm has adhesive properties which hold to the phospholipid bilayers tightly

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8
Q

What is Guillain-Barre Syndrome?

A

The demyelinating disease in the PNS

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9
Q

What is the demyelinating disease in the PNS?

A

Guillain-Barre Syndrome

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10
Q

What does the increased lipid content of the myelin sheath do?

A

Provides insulation for the underlying axon

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11
Q

What is myelin important for?

A

Allowing saltatory conduction of action potentials. Ensures conduction is not lost across the membrane

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12
Q

Which types of axons are always myelinated?

A

Motor axons

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13
Q

What would happen without myelin?

A

The sodium would dissipate laterally

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14
Q

How are unmyelinated axons in the PNS affected by myelin?

A

Unmyelinated axons in the PNS are encased by Schwann cell cell cytoplasm but no wrapped coating of myelin

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15
Q

What are Remak Bundles?

A

Unmyelinated axons in the PNS that are encased by Schwann cell cytoplasm but don’t have the wrapped coating of myelin

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16
Q

What is the ratio for Schwann cell myelination and axons?

A

One Schwann cell can ensheath multiple axons, but myelinates only one axon segment

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17
Q

How are small diameter nerve fibers affected by myelin?

A

Small diameter nerve fibres are non-myelinated

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18
Q

What are the three types of connective tissue layers found in nerves?

A

Endoneurium
Perineurium
Epineurium

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19
Q

What does endoneurium do?

A

Surrounds axons

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20
Q

What does perineurium do?

A

Surrounds axon fascicles

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21
Q

What does epineurium do?

A

Surrounds the entire nerve

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22
Q

What surrounds axons?

A

Endoneurium

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23
Q

What surrounds axon fascicles?

A

Perineurium

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24
Q

What surrounds an entire nerve?

A

Epineurium

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25
Q

Why do peripheral nerves have elastin?

A

Because they need to be able to stretch and move the same way the body does

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26
Q

Which neuron layer sits around the myelin sheath?

A

The endoneurium

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27
Q

What are the two types of ganglia?

A

Spinal Ganglia and Autonomic Ganglia

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28
Q

What are the two types of spinal ganglia?

A

Dorsal root and cranial ganglia

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29
Q

What are the dorsal root ganglia associated with?

A

Spinal nerves

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30
Q

What are the cranial ganglia associated with?

A

Cranial nerves

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31
Q

Does a synapse happen in ganglia?

A

No

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32
Q

What do spinal ganglia contain?

A

Large sensory neurons and abundant small glial cells called satellite cells

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33
Q

What are Satellite cells?

A

Cell bodies around sensory nerves

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34
Q

What kind of neurons are sensory neurons?

A

Pseudounipolar

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35
Q

What are autonomic ganglia?

A

The cell bodies of second-order neurons out in the peripheral nervous system

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36
Q

What are autonomic ganglia associated with?

A

Sympathetic and parasympathetic nervous systems

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37
Q

Does a synapse occur in autonomic ganglia?

A

Yes

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38
Q

Which ganglia does a synapse occur and what ganglia does a synapse not occur?

A

Spinal ganglia - no synapse
Autonomic ganglia - synapse

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39
Q

What kind of neurons are in autonomic ganglia?

A

Multipolar neurons

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40
Q

What is the difference in the type of neurons in the two ganglia?

A

Spinal ganglia - Pseudounipolar
Autonomic ganglia - Multipolar

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41
Q

What are sympathetic ganglion cells?

A

Multipolar neurons that reside entirely within the PNS in sympathetic ganglia and preaortic ganglia

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42
Q

Where do sympathetic ganglion cells reside?

A

In the PNS in the sympathetic chain ganglia

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43
Q

What are sensory receptors classified based on?

A

Source of stimulus

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44
Q

What are the three types of sensory receptors?

A
  • Exteroreceptors
  • Interoceptors/Visceroreceptors
  • Proprioceptors
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45
Q

What do Exteroreceptors respond to?

A

External stimuli (touch, temperature, pressure, sight, smell, taste, hearing)

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46
Q

What do Interoceptors/Visceroreceptors response to?

A

Stimuli within the body (respiration, cardiovascular, digestion, reproductive, urinary)

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47
Q

What do Proprioceptors respond to?

A

Interoceptors of muscle stretch and movement (tendons, ligament, joints, skeletal muscles, connective tissue covering the bones and muscles)

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48
Q

What are the four types of nerve fibers?

A
  • Aα
  • Aβ
  • Aδ
  • C
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49
Q

What are the largest diameter axons?

A

Aα

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50
Q

How is diameter correlated with myelination?

A

The larger the diameter, the more myelination the faster the axon

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51
Q

What do Aα fibers sense?

A

Proprioception

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52
Q

Which nerve fibers sense propriception?

A

Aα fibers

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53
Q

What are the fastest neurons in the body?

A

Aα neurons that sense proprioception

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54
Q

What are the most heavily myelinated axons?

A

Aα neurons

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55
Q

What do Aβ fibers sense?

A

Mechanoreceptors of skin (texture, touch, temperature)

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56
Q

Which fibers are mechanoreceptors of skin (touch receptors)?

A

Aβ fibers

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57
Q

What are the two pain-sensing afferents in the body?

A

Aδ and C fibers

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58
Q

What do Aδ and C fibers sense?

A

Pain

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59
Q

Which pain fibers are myelinated?

A

Aδ fibers

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60
Q

Which pain fibers are unmyelinated?

A

C

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61
Q

What kind of pain does Aδ fibers sense?

A

Sharp immediate pain

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62
Q

What kind of pain do C fibers sense?

A

Dull achy pain

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63
Q

Which fibers carry pain fastet?

A

Aδ fibers

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64
Q

Which pain fibers sense sharp pain?

A

Aδ pain

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65
Q

Which pain fibers sense dull pain?

A

C fibers

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66
Q

Which laminae of the spinal cord do Aδ fibers go to?

A

I or V

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67
Q

Which laminae of the spinal cord do C fibers go to?

A

II - substantia gelatinosa

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68
Q

Which pain fibers go to I or V?

A

Aδ fibers

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69
Q

Which pain fibers go to II?

A

C

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70
Q

Where in the periphery are Aβ, Aδ and C nerve fibers?

A

In the skin

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71
Q

What provides sensory information to muscles and tendons?

A

Aα

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72
Q

What other nerve fibers do motor nerves contain?

A

A𝛼 𝑎𝑛𝑑 𝐴𝛾

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73
Q

Why is it important for touch and proprioception fibers to be faster than pain?

A

Because we require touch information move ourselves from pain

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74
Q

What are the two main layers of the skin?

A

The epidermis and dermis

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75
Q

What is the basal layer of skin?

A

The stem cell layer

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76
Q

What do stem cell layers of skin make?

A

Keratinocytes

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77
Q

What happens as new keratinocyte is made?

A

They are pushed up away from their blood supply and release their nucleus, produce keratin and die

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78
Q

What is the purpose of keratin?

A

Keeps us from dehydrating and is a huge immune organ

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79
Q

What free nerve endings are in the skin?

A

C and Aδ fibers

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80
Q

What nerve fibers have free nerve endings?

A

C and Aδ fibers

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81
Q

What are the most superficial nerve endings?

A

Pain fibers

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82
Q

What are free nerve endings?

A

Nerve endings with nothing special at their termini, once there is a chemical release, they will initiate an action potential. (whereas mechanoreceptors require a certain stimulus)

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83
Q

Where do Merkel’s disks sit?

A

At the stem cell layer of the skin

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84
Q

What are Merkel’s disks?

A

Aβ receptors

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85
Q

What do Meissner’s corpuscles sense?

A

Mechanoreception

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86
Q

What are the mechanoreceptors in the skin?

A
  • Merkel’s disks
  • Meissner’s corpuscles
  • Pacinian corpuscles
  • Ruffini endings
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87
Q

What are arrector pili innervated by?

A

The autonomic nervous system

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88
Q

What are receptors in the skin classified based on?

A

Modality

89
Q

What are nociceptors classified base on?

A

Conduction velocity and noxious stimuli

90
Q

What are the five classes of receptors?

A
  1. Nociceptor
  2. Chemoreceptors
  3. Photoreceptors
  4. Thermoreceptors
  5. Mechanoreceptors
91
Q

What are mechanoreceptors classified based on?

A

Location and physical properties and rate of adaptation

92
Q

What are nociceptors involved in?

A

Perception of pain

93
Q

Which pain fibres are responsible for extremely sharp pain?

A

Aδ

94
Q

Which pain fibers are responsible for prolonged slightly intense and diffused pain?

A

C-fibers

95
Q

What are Aδ responsible for?

A

First phasic (initial) extremely sharp pain

96
Q

What are C-fibers responsible for?

A

second phasic, prolonged slightly intense and diffused pain as result of acute damage to the skin

97
Q

What are the different types of noxious stimuli?

A

Thermal
Mechanical
Chemical
Polymodal

98
Q

What do thermal noxious receptors respond to?

A

Respond to noxious heat and cold (>45°C or <5°C)

99
Q

What do mechanical noxious receptors respond to?

A

Excessive pressure

100
Q

What do chemical noxious receptors respond to?

A

respond to chemical substances (inflammatory mediators) from the surrounding damages tissue (histamine)

101
Q

What do Polymodal noxious receptors respond to?

A

High-intensity and prolonged stimuli such as thermal, mechanical and chemical stimuli

102
Q

When are silent or sleeping nociceptors activated?

A

Only at extreme intensity of mechanical stimulation or inflammation in the surrounding tissue

103
Q

What do Chemoreceptors detect?

A

Chemical stimuli

104
Q

What are examples of chemoreceptors?

A
  • Stimuli in the olfactory system
  • Stimuli in taste buds and aortic bodies (for sensing oxygen)
105
Q

What do photoreceptors respond to?

A

Light for vision

106
Q

What are Cones and Rods and ganglion cells receptive to?

A

Cones (color: red/yellow, green, blue)
Rods (sensitive to light intensity)
Ganglion cells (sympathetic response in adrenal medulla and retina)

107
Q

What do thermoreceptors respond to?

A

Innocuous temperature stimuli

108
Q

Which fibers do thermoreceptors work vis?

A

Group A and C fibers

109
Q

What to things are mechanoreceptors comprised of?

A

Exteroreceptors and proprioceptors

110
Q

What do mechanoreceptors receptors respond to?

A

Respond to touch, pressure, stretch, muscles, tendons, ligaments and joint capsules

111
Q

What do Merkel’s discs sense?

A

Touch

112
Q

Where are Merkel’s discs located?

A

Between dermis and epidermis

113
Q

What do Meissner Corpuscles sense?

A

Light touch

114
Q

Where are meissner’s corpuscles in the skin?

A

In the dermis near the epidermis

115
Q

What do Pacinian corpuscles sense?

A

Pressure

116
Q

Where are Pacinian corpuscles located?

A

In the subcutaneous fat of the dermis

117
Q

What do Ruffini’s endings sense?

A

Pressure and temperature

118
Q

What in the skin senses touch?

A

Merkel’s discs

119
Q

What in the skin sense light touch?

A

Meissners corpuscles

120
Q

What in the skin senses pressure?

A

Pacinian corpuscles

121
Q

What in the skin senses pressure and temperature?

A

Ruffini’s endings

122
Q

Which mechanoreceptors have a large receptive field?

A

Those that detect pressure

123
Q

What are the three rates of adaptation of mechanoreceptos?

A

Slow Adapting (SA)
Moderate Adapting (MA)
Rapidly Adapting (RA)

124
Q

What is a receptive field?

A

An area which when stimulated elicits a neuronal response

125
Q

What are the slow adapting mechanoreceptors?

A

Merkel’s discs and Ruffini’s endings

126
Q

What are the characteristics of slow adapting mechanoreceptors?

A

They are on and fire as long as a stimulus is present

127
Q

What fibers are moderate adapting?

A

Free nerve endings and D-hari (HFA)

128
Q

What is an example of something moderate adapting fibers may sense?

A

Insects on the skin

129
Q

What are examples of rapidly adapting fibers?

A

Meissner’s corpuscles and Pacinian corpuscles

130
Q

What are the characteristics of rapidly adapting fibers?

A

They respond to stimulation with a burst of firing in the beginning and end of stimulation

131
Q

What do Merkel receptors best respond to?

A

Steady pressure from small objects

132
Q

What do Meissner corpuscles best respond to?

A

Rubbing against the skin or skin movement across a surface

133
Q

What do Ruffini’s cylinders best respond to?

A

Steady pressure and stretching of the skin (e.g. joint movement)

134
Q

What do Pacinian corpuscle best respond to?

A

Changing stimulation

135
Q

What is Pain?

A

An unpleasant sensory and emotional experience associated with actual or potential damaged

136
Q

What best responds to steady pressure from small objects?

A

Merkel receptors

137
Q

What best responds to rubbing against the skin or skin or movement across a surface?

A

Meissner’s corpuscles

138
Q

What best responds to steady pressure and stretching of the skin (e.g. joint movement)?

A

Ruffini cylinders

139
Q

What best responds to changing stimulation?

A

Pacinian corpuscles

140
Q

What is nociceptive pain?

A

Pain arising from tissue damage (activation of nociceptors)

141
Q

What is inflammatory pain?

A

Pain arising by inflammation initiated by autoimmune response

142
Q

What is neuropathic pain?

A

Pain arising from nerve damage/somatosensory system

143
Q

What is Nociplastic pain?

A

Pain arising with no clear evidence of tissue damage

144
Q

What are examples of nociceptive pain?

A

Burns, fractures, lacerations

145
Q

What are examples of inflammatory pain?

A

Gout, rheumatoid arthritis

146
Q

What are examples of neuropathic pain?

A

Diabetic neuropathy, carpal tunnel syndrome, complex regional pain syndrome

147
Q

What are examples of nociplastic pain?

A

Fibromyalgia, chronic lower back pain, irritable bowel syndrome

148
Q

What are the nociceptors?

A

Predominantly free nerve ending of Aδ and C afferents

149
Q

What do nociceptors respond to?

A

Extremes of:
- Temperature stimuli - raising temperature >45º or <0º C
- Mechanical stimuli - excessive pressure/tension
- Chemical stimuli - endogenous (histamine, prostaglandin) or exogenous

150
Q

What extremes do Aδ respond to?

A

Mechanosensitive and thermal stimuli

151
Q

What extremes do C fibers respond to?

A

Mechanical, thermal, chemical stimuli

152
Q

Where are nociceptors found?

A

In all tissues of the body except the brain

153
Q

What nociceptive fibers are myelinated?

A

Aδ are mylinated

154
Q

What happens if one of the pain fibers is blocked?

A

The first or second pain (depending on which one is blocked) will still be felt

155
Q

What are the steps in nociception?

A
  1. A stimulus activates a transient receptor potential (TRP) channels on C and Aδ fibers
  2. This causes a 6 membrane pore to open
  3. This allows an influx of Na and Ca which generates an action potential which propagates to the spinal cord
156
Q

Through which types of cells do pain action potentials propogate?

A

Pseudounipolar

157
Q

What are two types of clinical pain conditions?

A
  • Congenital Insensitivity to Pain (CIP)
  • Paroxysmal Extreme Pain Disorder (PEPD)
158
Q

What is Congenital Insensitivity to Pain (CIP)?

A

The inability to perceive pain and anhidrosis (inability to sweat)

159
Q

What is Paroxysmal Extreme Pain Disorder (PEPD)?

A

Burning pain in rectum, eyes, mandible but can be diffuse pain

160
Q

What causes the two pain disorders?

A

Mutation of SCN9A gene → Nav 1.7 channelopathy

161
Q

What is Nav 1.7?

A

Voltage-gated sodium channel on nociceptors for action potential propagation

162
Q

How are the channels affected in CIP?

A

channel is nonfunctional → no action potential initiation

163
Q

How are the channels affected in PEPD?

A

channel opens at a lesser membrane depolarization or stays open too long → increased pain

164
Q

What is the sensory part of the spinal cord?

A

The dorsal horn

165
Q

Which three pathways enter the dorsal horn of the spinal cord?

A
  • Dorsal column medial lemniscal pathway
  • Spinothalamic tract
  • Spinocerebellar tract
166
Q

Through what tract do the the sensory pathways enter the dorsal horn?

A

Lissauer’s tract

167
Q

What is Lissauer’s tract?

A

The entrance of the dorsal roots into the spinal cord

168
Q

What laminae do C fibers enter the spinal cord?

A

Laminae 1 and 2 (Substantia Gelatinosa)

169
Q

What laminae do Aδ fibers enter the spinal cord?

A

Laminae 1 and 5

170
Q

Which laminae do the pain fibers enter the spinal cord?

A
  • C fiber afferents: laminae 1 and 2 (substantia gelatinosa)
  • Aδ fiber afferents: laminae 1 and 5
171
Q

Where in the spinothalamic pathway is the decussation in synapsing?

A
  • First order neurons synapse in the spinal cord
  • The second order neurons decussate and ascend to the VPL of the thalamus and synapse
  • The then go to the primary somatosensory cortex
172
Q

How many neurons are in the pain pathways?

A

Three neurons

173
Q

Which nuclei in the thalamus does the pain pathway synapse?

A

The VPL nucleus

174
Q

Where does the second order neuron in the spinothalamic pathway send its axons?

A

To the VPL nucleus of the thalamus and collateral branches

175
Q

What are the five pain intiators?

A
  • Glutamate
  • Calcitonin gene related peptides (CGRP)
  • Substance P
  • Bradykinin
  • Prostaglandin
176
Q

What is the pain initiatory for Aδ fibers?

A

Glutamate

177
Q

What does substance P do in the pain pathway?

A

It is released by the first-order neuron onto the second-order neuron in the spinothalamic tract

178
Q

What are the two inflammatory pain initiators?

A

Bradykinin and prostaglandin

179
Q

What are the seven pain inhibitors?

A
  • Serotonin
  • Somatostatin
  • Endorphins
  • Enkephalins
  • Dynorphins
  • GABA
  • Glycine
180
Q

Where in the brain is Serotonin?

A

In the raphe nucleus

181
Q

What are the three endogenous opioids?

A
  • Endorphins
  • Enkephalins
  • Dynorphins
182
Q

When does the second-order neuron in the pain pathway send collateral branches?

A

When it reaches the brainstem

183
Q

What does VPL stand for?

A

Ventral posterior lateral nucleus

184
Q

What is the neuron pathway of the dorsal column medial lemniscal pathway?

A
  • first-order neuron goes from receptor, ascends the dorsal column in the spinal cord to the medulla. It synapses at the medulla
  • Second order neuron decussates and goes from the medulla to thalamus
  • Third order neuron goes from the thalamus to the somatic sensory cortex
185
Q

What is Brown Séquard Syndrome?

A

A lesion to half of the spinal cord so an individual can’t feel pain and temperature on one side and can’t feel touch and proprioception on the other side

186
Q

In Brown Séquard Syndrome what does injury to the left hemicord cause?

A
  • Loss of pain/temperature on right side below lesion
  • Loss of touch, vibration, proprioception on left side below lesion
187
Q

Aside from the somatosensory cortex, where does the spinothalamic pathway project to?

A
  • Amygdala
  • Hypothalamus
  • Periaqueductal gray
  • Reticular formation
  • Superior Colliculus
188
Q

What does the spinothalamic pathway projecting to the Amygdala affect?

A

Memory and emotion

189
Q

What does the spinothalamic pathway projecting to the Hypothalamus affect?

A

Activation of the autonomic nervous system

190
Q

What does the spinothalamic pathway projecting to the reticular formation affect?

A

It controls the raphe nuclei which produces serotonin

191
Q

What does the spinothalamic pathway projecting to the reticular activating system affect?

A

Alertness during pain

192
Q

What does the sensory/discriminative portion of the pain pathway do?

A

Observes the location, intensity, and quality of pain

193
Q

What are the two pain suppression systems?

A
  • Gate control hypothesis
  • Supraspinal pain suppression
194
Q

What is the form of spinal pain suppression?

A

Gate control hypothesis

195
Q

What is the form of supraspinal pain suppession?

A

Descending serotonergic and opioid inhibitory system

196
Q

What idea does gate control theory act on?

A

Pressure stops pain

197
Q

How does gate control theory work?

A
  1. Both A-beta (touch) and C fibers (pain) enter Lissauer’s tract
  2. A- beta fibers stimulate inhibitory interneurons. C fibers inhibit inhibitory interneurons
  3. A-beta fibers inhibit pain pathways and C fibers stimulate pain pathways
198
Q

Which order neurons does gate control theory act on?

A

The second order neuron

199
Q

How does Descending control of pain modulation work?

A
  1. Spinothalamic tract sends collateral branches to the spinomesencephalic tract
  2. The spinomesencephalic tract activates the periaqueductal grey
  3. This turns on descending inputs to the raphe nucleus
  4. The raphe nucleus sends serotonergic projections that release endogenous opioids onto the first order neuron in the spinothalamic pathway to prevent it from releasing substance P onto the second order neuron
200
Q

What is the first step in the descending pain modulation pathway?

A

The spinothalamic tract activates the spinomesencephalic pathway

201
Q

What happens after the spinomesencephalic pathway is activated in the descending pain modulation pathway?

A

It sends descending inputs to the raphe nucleus

202
Q

What happens after the spinomesencephalic nucleus sends descedning input to the raphe nucleus?

A

The raphe nucleus sends serotonergic fibers down to release endogenous opioid onto the first order neuron in the spinothalamic pathway to prevent it from releasing substance P onto the second order neurons

203
Q

What do the endogenous opioids released by the serotonergic neurons of the raphe nucleus do?

A

They act on mu and kappa opioid receptors on C fibers and A delta fibers preventing them from releasing substance P onto the second order neuron to activate it

204
Q

What order neuron does the descending pain pathway act on?

A

The first order neuron

205
Q

What is chronic pain?

A

Pain that persists past the normal healing time

206
Q

What is hyperalgesia?

A

Increased pain sensation from a normally painful stimulus

207
Q

What is Hyperestheisa?

A

Increased sensitivity to stimulation

208
Q

What is Allodynia?

A

Perception of pain from non-noxious stimulus

209
Q

What is Dysesthesia?

A

Unpleasant abnormal sensation

210
Q

What are the two mechanisms of sensitization in chronic pain?

A

Peripheral sensitization and central sensitization

211
Q

What is peripheral sensitization?

A

The upregulation of existing receptors or making new receptors that activate C and A-delta fibers caused by cytokines. Makes an individual sensitive to stimuli.

212
Q

How can peripheral sensitization be reduced?

A

NSAIDs which reduce COX and with Antihistamines

213
Q

What is central sensitization?

A

Either a hypersensitivity or a responsiveness to non-noxious stimuli. An enlarged receptive field

214
Q

What is a neuroma?

A

When a transected peripheral nerve attempts to regenerate to establish contact with motor or sensory end organs but instead forms a ball that activates itself causing pain

215
Q

Why does a neuroma forma a balck?

A

Because it lacks an epineurium which will guide it on where to go

216
Q

What are the two ways to manage neuromas?

A

Targeted motor reinnervation (TMR) and Regenerative Peripheral Nerve Interface (RPNI)

217
Q

What occurs in Target Motor Reinnervation?

A

Distal ends of mixed nerves or sensory nerves transferred to motor nerve of a nearby muscle target

218
Q

What occurs in Regenerative Peripheral Nerve Interface (RPNI)

A

Implant distal end of nerve into a free skeletal muscle graft

Neuro 3 (21 decks)

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