Lecture 18: Pain (peripheral nervous system pain) Flashcards
1
Q
What is conduction velocity in an axon enhanced by?
A
Myelination
2
Q
What does myelination do?
A
Enhances conduction velocity in an axon
3
Q
What are axons in the CNS mylinated by?
A
Oligodendrocytes
4
Q
What do oligodendrocytes mylinate?
A
Axons in the CNS
5
Q
What myelinates axons in the PNS?
A
Schwann cells
6
Q
What do Schwann cells do?
A
Myelinate axons in the PNS
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
8
Q
What is Guillain-Barre Syndrome?
A
The demyelinating disease in the PNS
9
Q
What is the demyelinating disease in the PNS?
A
Guillain-Barre Syndrome
10
Q
What does the increased lipid content of the myelin sheath do?
A
Provides insulation for the underlying axon
11
Q
What is myelin important for?
A
Allowing saltatory conduction of action potentials. Ensures conduction is not lost across the membrane
12
Q
Which types of axons are always myelinated?
A
Motor axons
13
Q
What would happen without myelin?
A
The sodium would dissipate laterally
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
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
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
17
Q
How are small diameter nerve fibers affected by myelin?
A
Small diameter nerve fibres are non-myelinated
18
Q
What are the three types of connective tissue layers found in nerves?
A
Endoneurium
Perineurium
Epineurium
19
Q
What does endoneurium do?
A
Surrounds axons
20
Q
What does perineurium do?
A
Surrounds axon fascicles
21
Q
What does epineurium do?
A
Surrounds the entire nerve
22
Q
What surrounds axons?
A
Endoneurium
23
Q
What surrounds axon fascicles?
A
Perineurium
24
Q
What surrounds an entire nerve?
A
Epineurium
25
Why do peripheral nerves have elastin?
Because they need to be able to stretch and move the same way the body does
26
Which neuron layer sits around the myelin sheath?
The endoneurium
27
What are the two types of ganglia?
Spinal Ganglia and Autonomic Ganglia
28
What are the two types of spinal ganglia?
Dorsal root and cranial ganglia
29
What are the dorsal root ganglia associated with?
Spinal nerves
30
What are the cranial ganglia associated with?
Cranial nerves
31
Does a synapse happen in ganglia?
No
32
What do spinal ganglia contain?
Large sensory neurons and abundant small glial cells called satellite cells
33
What are Satellite cells?
Cell bodies around sensory nerves
34
What kind of neurons are sensory neurons?
Pseudounipolar
35
What are autonomic ganglia?
The cell bodies of second-order neurons out in the peripheral nervous system
36
What are autonomic ganglia associated with?
Sympathetic and parasympathetic nervous systems
37
Does a synapse occur in autonomic ganglia?
Yes
38
Which ganglia does a synapse occur and what ganglia does a synapse not occur?
Spinal ganglia - no synapse
Autonomic ganglia - synapse
39
What kind of neurons are in autonomic ganglia?
Multipolar neurons
40
What is the difference in the type of neurons in the two ganglia?
Spinal ganglia - Pseudounipolar
Autonomic ganglia - Multipolar
41
What are sympathetic ganglion cells?
Multipolar neurons that reside entirely within the PNS in sympathetic ganglia and preaortic ganglia
42
Where do sympathetic ganglion cells reside?
In the PNS in the sympathetic chain ganglia
43
What are sensory receptors classified based on?
Source of stimulus
44
What are the three types of sensory receptors?
- Exteroreceptors
- Interoceptors/Visceroreceptors
- Proprioceptors
45
What do Exteroreceptors respond to?
External stimuli (touch, temperature, pressure, sight, smell, taste, hearing)
46
What do Interoceptors/Visceroreceptors response to?
Stimuli within the body (respiration, cardiovascular, digestion, reproductive, urinary)
47
What do Proprioceptors respond to?
Interoceptors of muscle stretch and movement (tendons, ligament, joints, skeletal muscles, connective tissue covering the bones and muscles)
48
What are the four types of nerve fibers?
- Aα
- Aβ
- Aδ
- C
49
What are the largest diameter axons?
Aα
50
How is diameter correlated with myelination?
The larger the diameter, the more myelination the faster the axon
51
What do Aα fibers sense?
Proprioception
52
Which nerve fibers sense propriception?
Aα fibers
53
What are the fastest neurons in the body?
Aα neurons that sense proprioception
54
What are the most heavily myelinated axons?
Aα neurons
55
What do Aβ fibers sense?
Mechanoreceptors of skin (texture, touch, temperature)
56
Which fibers are mechanoreceptors of skin (touch receptors)?
Aβ fibers
57
What are the two pain-sensing afferents in the body?
Aδ and C fibers
58
What do Aδ and C fibers sense?
Pain
59
Which pain fibers are myelinated?
Aδ fibers
60
Which pain fibers are unmyelinated?
C
61
What kind of pain does Aδ fibers sense?
Sharp immediate pain
62
What kind of pain do C fibers sense?
Dull achy pain
63
Which fibers carry pain fastet?
Aδ fibers
64
Which pain fibers sense sharp pain?
Aδ pain
65
Which pain fibers sense dull pain?
C fibers
66
Which laminae of the spinal cord do Aδ fibers go to?
I or V
67
Which laminae of the spinal cord do C fibers go to?
II - substantia gelatinosa
68
Which pain fibers go to I or V?
Aδ fibers
69
Which pain fibers go to II?
C
70
Where in the periphery are Aβ, Aδ and C nerve fibers?
In the skin
71
What provides sensory information to muscles and tendons?
Aα
72
What other nerve fibers do motor nerves contain?
A𝛼 𝑎𝑛𝑑 𝐴𝛾
73
Why is it important for touch and proprioception fibers to be faster than pain?
Because we require touch information move ourselves from pain
74
What are the two main layers of the skin?
The epidermis and dermis
75
What is the basal layer of skin?
The stem cell layer
76
What do stem cell layers of skin make?
Keratinocytes
77
What happens as new keratinocyte is made?
They are pushed up away from their blood supply and release their nucleus, produce keratin and die
78
What is the purpose of keratin?
Keeps us from dehydrating and is a huge immune organ
79
What free nerve endings are in the skin?
C and Aδ fibers
80
What nerve fibers have free nerve endings?
C and Aδ fibers
81
What are the most superficial nerve endings?
Pain fibers
82
What are free nerve endings?
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)
83
Where do Merkel's disks sit?
At the stem cell layer of the skin
84
What are Merkel's disks?
Aβ receptors
85
What do Meissner's corpuscles sense?
Mechanoreception
86
What are the mechanoreceptors in the skin?
- Merkel’s disks
- Meissner's corpuscles
- Pacinian corpuscles
- Ruffini endings
87
What are arrector pili innervated by?
The autonomic nervous system
88
What are receptors in the skin classified based on?
Modality
89
What are nociceptors classified base on?
Conduction velocity and noxious stimuli
90
What are the five classes of receptors?
1. Nociceptor
2. Chemoreceptors
3. Photoreceptors
4. Thermoreceptors
5. Mechanoreceptors
91
What are mechanoreceptors classified based on?
Location and physical properties and rate of adaptation
92
What are nociceptors involved in?
Perception of pain
93
Which pain fibres are responsible for extremely sharp pain?
Aδ
94
Which pain fibers are responsible for prolonged slightly intense and diffused pain?
C-fibers
95
What are Aδ responsible for?
First phasic (initial) extremely sharp pain
96
What are C-fibers responsible for?
second phasic, prolonged slightly intense and diffused pain as result of acute damage to the skin
97
What are the different types of noxious stimuli?
Thermal
Mechanical
Chemical
Polymodal
98
What do thermal noxious receptors respond to?
Respond to noxious heat and cold (>45°C or <5°C)
99
What do mechanical noxious receptors respond to?
Excessive pressure
100
What do chemical noxious receptors respond to?
respond to chemical substances (inflammatory mediators) from the surrounding damages tissue (histamine)
101
What do Polymodal noxious receptors respond to?
High-intensity and prolonged stimuli such as thermal, mechanical and chemical stimuli
102
When are silent or sleeping nociceptors activated?
Only at extreme intensity of mechanical stimulation or inflammation in the surrounding tissue
103
What do Chemoreceptors detect?
Chemical stimuli
104
What are examples of chemoreceptors?
- Stimuli in the olfactory system
- Stimuli in taste buds and aortic bodies (for sensing oxygen)
105
What do photoreceptors respond to?
Light for vision
106
What are Cones and Rods and ganglion cells receptive to?
Cones (color: red/yellow, green, blue)
Rods (sensitive to light intensity)
Ganglion cells (sympathetic response in adrenal medulla and retina)
107
What do thermoreceptors respond to?
Innocuous temperature stimuli
108
Which fibers do thermoreceptors work vis?
Group A and C fibers
109
What to things are mechanoreceptors comprised of?
Exteroreceptors and proprioceptors
110
What do mechanoreceptors receptors respond to?
Respond to touch, pressure, stretch, muscles, tendons, ligaments and joint capsules
111
What do Merkel's discs sense?
Touch
112
Where are Merkel's discs located?
Between dermis and epidermis
113
What do Meissner Corpuscles sense?
Light touch
114
Where are meissner's corpuscles in the skin?
In the dermis near the epidermis
115
What do Pacinian corpuscles sense?
Pressure
116
Where are Pacinian corpuscles located?
In the subcutaneous fat of the dermis
117
What do Ruffini's endings sense?
Pressure and temperature
118
What in the skin senses touch?
Merkel's discs
119
What in the skin sense light touch?
Meissners corpuscles
120
What in the skin senses pressure?
Pacinian corpuscles
121
What in the skin senses pressure and temperature?
Ruffini's endings
122
Which mechanoreceptors have a large receptive field?
Those that detect pressure
123
What are the three rates of adaptation of mechanoreceptos?
Slow Adapting (SA)
Moderate Adapting (MA)
Rapidly Adapting (RA)
124
What is a receptive field?
An area which when stimulated elicits a neuronal response
125
What are the slow adapting mechanoreceptors?
Merkel's discs and Ruffini's endings
126
What are the characteristics of slow adapting mechanoreceptors?
They are on and fire as long as a stimulus is present
127
What fibers are moderate adapting?
Free nerve endings and D-hari (HFA)
128
What is an example of something moderate adapting fibers may sense?
Insects on the skin
129
What are examples of rapidly adapting fibers?
Meissner's corpuscles and Pacinian corpuscles
130
What are the characteristics of rapidly adapting fibers?
They respond to stimulation with a burst of firing in the beginning and end of stimulation
131
What do Merkel receptors best respond to?
Steady pressure from small objects
132
What do Meissner corpuscles best respond to?
Rubbing against the skin or skin movement across a surface
133
What do Ruffini's cylinders best respond to?
Steady pressure and stretching of the skin (e.g. joint movement)
134
What do Pacinian corpuscle best respond to?
Changing stimulation
135
What is Pain?
An unpleasant sensory and emotional experience associated with actual or potential damaged
136
What best responds to steady pressure from small objects?
Merkel receptors
137
What best responds to rubbing against the skin or skin or movement across a surface?
Meissner's corpuscles
138
What best responds to steady pressure and stretching of the skin (e.g. joint movement)?
Ruffini cylinders
139
What best responds to changing stimulation?
Pacinian corpuscles
140
What is nociceptive pain?
Pain arising from tissue damage (activation of nociceptors)
141
What is inflammatory pain?
Pain arising by inflammation initiated by autoimmune response
142
What is neuropathic pain?
Pain arising from nerve damage/somatosensory system
143
What is Nociplastic pain?
Pain arising with no clear evidence of tissue damage
144
What are examples of nociceptive pain?
Burns, fractures, lacerations
145
What are examples of inflammatory pain?
Gout, rheumatoid arthritis
146
What are examples of neuropathic pain?
Diabetic neuropathy, carpal tunnel syndrome, complex regional pain syndrome
147
What are examples of nociplastic pain?
Fibromyalgia, chronic lower back pain, irritable bowel syndrome
148
What are the nociceptors?
Predominantly free nerve ending of Aδ and C afferents
149
What do nociceptors respond to?
Extremes of:
- Temperature stimuli - raising temperature >45º or <0º C
- Mechanical stimuli - excessive pressure/tension
- Chemical stimuli - endogenous (histamine, prostaglandin) or exogenous
150
What extremes do Aδ respond to?
Mechanosensitive and thermal stimuli
151
What extremes do C fibers respond to?
Mechanical, thermal, chemical stimuli
152
Where are nociceptors found?
In all tissues of the body except the brain
153
What nociceptive fibers are myelinated?
Aδ are mylinated
154
What happens if one of the pain fibers is blocked?
The first or second pain (depending on which one is blocked) will still be felt
155
What are the steps in nociception?
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
Through which types of cells do pain action potentials propogate?
Pseudounipolar
157
What are two types of clinical pain conditions?
- Congenital Insensitivity to Pain (CIP)
- Paroxysmal Extreme Pain Disorder (PEPD)
158
What is Congenital Insensitivity to Pain (CIP)?
The inability to perceive pain and anhidrosis (inability to sweat)
159
What is Paroxysmal Extreme Pain Disorder (PEPD)?
Burning pain in rectum, eyes, mandible but can be diffuse pain
160
What causes the two pain disorders?
Mutation of SCN9A gene → Nav 1.7 channelopathy
161
What is Nav 1.7?
Voltage-gated sodium channel on nociceptors for action potential propagation
162
How are the channels affected in CIP?
channel is nonfunctional → no action potential initiation
163
How are the channels affected in PEPD?
channel opens at a lesser membrane depolarization or stays open too long → increased pain
164
What is the sensory part of the spinal cord?
The dorsal horn
165
Which three pathways enter the dorsal horn of the spinal cord?
- Dorsal column medial lemniscal pathway
- Spinothalamic tract
- Spinocerebellar tract
166
Through what tract do the the sensory pathways enter the dorsal horn?
Lissauer's tract
167
What is Lissauer's tract?
The entrance of the dorsal roots into the spinal cord
168
What laminae do C fibers enter the spinal cord?
Laminae 1 and 2 (Substantia Gelatinosa)
169
What laminae do Aδ fibers enter the spinal cord?
Laminae 1 and 5
170
Which laminae do the pain fibers enter the spinal cord?
- C fiber afferents: laminae 1 and 2 (substantia gelatinosa)
- Aδ fiber afferents: laminae 1 and 5
171
Where in the spinothalamic pathway is the decussation in synapsing?
- 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
How many neurons are in the pain pathways?
Three neurons
173
Which nuclei in the thalamus does the pain pathway synapse?
The VPL nucleus
174
Where does the second order neuron in the spinothalamic pathway send its axons?
To the VPL nucleus of the thalamus and collateral branches
175
What are the five pain intiators?
- Glutamate
- Calcitonin gene related peptides (CGRP)
- Substance P
- Bradykinin
- Prostaglandin
176
What is the pain initiatory for Aδ fibers?
Glutamate
177
What does substance P do in the pain pathway?
It is released by the first-order neuron onto the second-order neuron in the spinothalamic tract
178
What are the two inflammatory pain initiators?
Bradykinin and prostaglandin
179
What are the seven pain inhibitors?
- Serotonin
- Somatostatin
- Endorphins
- Enkephalins
- Dynorphins
- GABA
- Glycine
180
Where in the brain is Serotonin?
In the raphe nucleus
181
What are the three endogenous opioids?
- Endorphins
- Enkephalins
- Dynorphins
182
When does the second-order neuron in the pain pathway send collateral branches?
When it reaches the brainstem
183
What does VPL stand for?
Ventral posterior lateral nucleus
184
What is the neuron pathway of the dorsal column medial lemniscal pathway?
- 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
What is Brown Séquard Syndrome?
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
In Brown Séquard Syndrome what does injury to the left hemicord cause?
- Loss of pain/temperature on right side below lesion
- Loss of touch, vibration, proprioception on left side below lesion
187
Aside from the somatosensory cortex, where does the spinothalamic pathway project to?
- Amygdala
- Hypothalamus
- Periaqueductal gray
- Reticular formation
- Superior Colliculus
188
What does the spinothalamic pathway projecting to the Amygdala affect?
Memory and emotion
189
What does the spinothalamic pathway projecting to the Hypothalamus affect?
Activation of the autonomic nervous system
190
What does the spinothalamic pathway projecting to the reticular formation affect?
It controls the raphe nuclei which produces serotonin
191
What does the spinothalamic pathway projecting to the reticular activating system affect?
Alertness during pain
192
What does the sensory/discriminative portion of the pain pathway do?
Observes the location, intensity, and quality of pain
193
What are the two pain suppression systems?
- Gate control hypothesis
- Supraspinal pain suppression
194
What is the form of spinal pain suppression?
Gate control hypothesis
195
What is the form of supraspinal pain suppession?
Descending serotonergic and opioid inhibitory system
196
What idea does gate control theory act on?
Pressure stops pain
197
How does gate control theory work?
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
Which order neurons does gate control theory act on?
The second order neuron
199
How does Descending control of pain modulation work?
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
What is the first step in the descending pain modulation pathway?
The spinothalamic tract activates the spinomesencephalic pathway
201
What happens after the spinomesencephalic pathway is activated in the descending pain modulation pathway?
It sends descending inputs to the raphe nucleus
202
What happens after the spinomesencephalic nucleus sends descedning input to the raphe nucleus?
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
What do the endogenous opioids released by the serotonergic neurons of the raphe nucleus do?
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
What order neuron does the descending pain pathway act on?
The first order neuron
205
What is chronic pain?
Pain that persists past the normal healing time
206
What is hyperalgesia?
Increased pain sensation from a normally painful stimulus
207
What is Hyperestheisa?
Increased sensitivity to stimulation
208
What is Allodynia?
Perception of pain from non-noxious stimulus
209
What is Dysesthesia?
Unpleasant abnormal sensation
210
What are the two mechanisms of sensitization in chronic pain?
Peripheral sensitization and central sensitization
211
What is peripheral sensitization?
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
How can peripheral sensitization be reduced?
NSAIDs which reduce COX and with Antihistamines
213
What is central sensitization?
Either a hypersensitivity or a responsiveness to non-noxious stimuli. An enlarged receptive field
214
What is a neuroma?
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
Why does a neuroma forma a balck?
Because it lacks an epineurium which will guide it on where to go
216
What are the two ways to manage neuromas?
Targeted motor reinnervation (TMR) and Regenerative Peripheral Nerve Interface (RPNI)
217
What occurs in Target Motor Reinnervation?
Distal ends of mixed nerves or sensory nerves transferred to motor nerve of a nearby muscle target
218
What occurs in Regenerative Peripheral Nerve Interface (RPNI)
Implant distal end of nerve into a free skeletal muscle graft
