Nociception (Exam 2) Flashcards
(205 cards)
1
Q
T/F
Transduction always refers to a painful stimulus.
A
False
Transdxn doesn’t necessarily mean painful; refers to converting into electrical impulse
2
Q
Transduction
A
noxious stimuli (e.g., heat, cold, mechanical distortion)
⬇️
electrical impulse in sensory nerve endings
3
Q
Whorls
A
spiral shape seen at end of sensory dendrite; deform/compress triggers signal to travel down dendrite to body (senses pressure)
4
Q
Whorls sense what type of stimulus?
A
pressure
5
Q
How does increasing T affect receptors?
A
can open and allow NA in»_space; allows stimulation
process of sensing heat
6
Q
Sensing heat causes an influx of ___
A
Na
7
Q
Tissue damage results in release of ___ ions, which can open certain receptors.
A
H+
8
Q
Transmission
A
conduction of these electrical impulses to the CNS
major connections:
-dorsal horn (SC)
-thalamus with projections to the cingulate, insular, and somatosensory cortices.
9
Q
Process of transmission
A
-Nerves enter dorsal horn (SC)
⬇️
projection pathways (somatosensory pathways)
⬇️
up SC
⬇️
brain
⬇️
branch off in certain places, esp the thalamus
10
Q
Transmission
major connections:
A
-dorsal horn (SC)
-thalamus with projections to the cingulate, insular, and somatosensory cortices.
(T ➡️ CIS
Thalamus to Cingulate, Insular, Somatosensory)
11
Q
Relay center for incoming pain signals
A
Thalamus
receive input; synapse to others ie neocortex
12
Q
Levels of consciousness are found in
A
the cerebral cortex
13
Q
Which cortices are a/w:
lower brain levels & emotional responses
A
cingulate, insular
14
Q
Which cortices are a/w:
bringing things into consciousness
A
somatosensory
15
Q
Modulation
Alters which stage of nociception?
A
altering pain transmission
inhibitory & excitatory mechanisms modulate pain/nociceptive impulse transmission in the PNS and CNS
16
Q
T/F
mechanisms modulate pain/nociceptive impulse transmission in the PNS and CNS are inhibitory
A
False
inhibitory & excitatory
17
Q
sensation of pain
A
nociception
18
Q
Perception
mediated thru…
A
thalamus: central relay station for incoming pain signals
primary somatosensory cortex: discrimination of specific sensory experiences
19
Q
T/F
Modulation can relieve pain
A
True
Severe sudden pain will shift focus almost 100% to it
Not sustainable
So we modulate pain immediately
Pain relieving in a sense
20
Q
Perception
A
bringing pain into consciousness to process and make decision
21
Q
primary somatosensory cortex
A
discrimination of specific sensory experiences
What pain is it? Biggie or no biggie? Where from?
22
Q
all or nothing response
A
axon only has one choice: fire or dont
signal traveling down axon
axon can only signal down or not
23
Q
Temporal signaling
A
(down an axon)
firing rate
24
Q
T/F
There is no required time frame between an axon firing.
A
False
takes time for axon to reset and send another signal
minimum period of time between firing
25
Cells adjacent to an axon are sensing...
a time/signal pattern
a cell may only respond to a certain firing rate/pattern
26
the only way nerves can signal each other
temporal signaling
27
Very painful stimuli firing rate
very rapid
(type 1 neurons)
28
Firing rates/patterns:
Type I neuron vs. Type II neuron
Type I: more linear; can alter firing rate
Type II: have different patterns
29
discrimination of sensory experience is based on:
-which nerves fire
-rate/pattern of firing
30
Stepping on a lego vs marshmallow
The response is dependent on...
temporal signaling
(firing pattern)
31
The 4 components of Nociception
Transduction
Transmission
Modulation
Perception
32
T/F
Pain can only occur when all 4 components of nociception occur.
False
pain can occur without one or more of these steps
(ex: **phantom limb pain**)
33
phantom limb "pain"
Not always pain; sometimes just sensation
d/t higher processing neurons still responding/firing w/o stimuli
(not getting the stimuli they used to get but still firing)
34
T/F
phantom limb "pain" is d/t the hypersensitivity of the remaining sensory neurons.
False
d/t higher processing neurons still responding/firing w/o the original stimuli
35
C-fiber afferents
(unmyelinated & slowest conduction)
burning
sustained pressure
36
Type I fibers
(some Aβ and some Aδ)
myelinated
"polymodal fibers"
thermal, chemical & mechanical stimuli
37
T/F
Thermal pain is not the same as burning pain
True
38
Consistent firing in-between transmissions; only “pattern” is speeding up/slowing down (linear)
Type I fibers (some Aβ and some Aδ) "polymodal fibers"
39
T/F
Type I fibers respond to a single stimulus.
False
called "polymodal" bc they respond to multiple things
40
Thermal vs burning pain
burning = instantaneous pain
thermal = consistent, longer-term response
41
Non-linear/ "saddle transmission"
Type II fibers (some Aδ fibers; slower)
bizarre patterns
can also speed up and slow down
42
can signal pain from chemical and cold stimuli
Both myelinated and unmyelinated
43
Type II fibers
(some Aδ fibers; slower)
initial pain responses to heat
non-linear
bizarre patterns
44
Myelination is more critical to (motor/sensory) fxn.
motor
**M**yelinated **M**otor
45
"Capsation" receptor is a/w what sensation
burning
46
Capsation/Vanilloid Receptor/ Transient V receptor-1 (TVR1)
structure
Voltage gated
4 subunit
similar to NMDA
47
Capsation/Vanilloid (VR1) Receptor/ Transient V receptor-1 (TVR1)
MoA
Na & Ca in; K out
depending on state of neuron
scalding heat and pain
activated/augmented by:
PKC, PKA, Ca
48
PIP is located in ___ and can be broken down into ....
cell membrane
DAG & IP3
49
T/F
Prostaglandins and bradykinins are known to cause pain
False
do not cause
but
worsen/augment pain
50
substances that transmit pain when released from neurons
CGRP (Calcitonin gene-related peptide)
SP (substance P)
glutamate
51
T/F
Ca release aids in pain transmission
True
Ca stimulates NT release into synapse and communicates pain
52
What stimulates Ca release?
-Depolarization (Na influx)
-IP3
-PK3
-PKC
53
T/F
PKA stimulates Ca release and pain transmission
False
stimulates Ca release:
-Depolarization (Na influx)
-IP3
-PK3
-PKC
54
Role of bradykinin in pain
increases IP3 >> Ca release >> NT release
increases DAG >> PKC >> Ca >> NT release
Augments pain, doesn’t cause it
55
Role of PGE2 in pain
(Prostaglandin E2)
increased cAMP > activates PKA > Na influx > depolarization > Ca release > NT release
56
Activates Na (depolarization)
PKC
PKA
57
Which substances act here to inhibit pain?
Endorphins
ACh
cannabinoids
58
Which act via G protein complexes?
Endorphins
ACh
cannabinoids
All
stimulate K channels
K out
hyperpolarize
59
cAMP role in nociceptive signal transduction
Increase cAMP = alter PKA = stimulate Na ion entry = depolarization & passage of signal
60
increase of cAMP will directly...
increase/alter PKA
end result: Na influx & depolarization
61
released from *some* sensory nerves as a means of pain transmission
Calcitonin gene-related peptide (CGRP)
Substance P (SP)
62
Substance P (SP)
**undeca**peptide
acts at Neurokinin-1 receptors (NK-1) (amygdala, hypothalamus, & periaqueductal gray)
63
brings pain into emotional consciousness
amygdala
64
"P" in SP stands for
powder
65
SP is found with ___ in __ __ that respond to painful stimuli
glutamate
primary afferents
66
Neurokinin-1 receptors (NK-1)
widely distributed in the brain
in areas a/with pain processing:
amygdala, hypothalamus, & periaqueductal gray
SP acts on this site
67
specific areas associated with pain processing
amygdala, hypothalamus, and periaqueductal gray
68
An NK-1 receptor antagonist would block...
Substance P
SP: undecapeptide that acts at Neurokinin-1 receptors (NK-1)
69
Aside from nociceptive pain transduction, CGRP causes ___
vasodilation
decreases BP
70
CGRP antagonist
MoA
attenuates the increase in BP (that causes migraine) and block pain
71
Gi/o receptor
"G inhibitory"
Inhibitory opioid receptor
inhibitory actions at pain receptors
Causes receptor hyperpolarization by increasing potassium conductance (K out)
72
T/F
Endorphin, cannabinoid, and acetylcholine receptors are examples of Transient V receptor-1 (TVR1)
False
Gi/o receptor system
hyperpolarization by increasing potassium conductance
73
Provides sensations of scalding heat and pain
Transient V receptor-1 (TVR1)
"Capsaicin/Vanilloid receptor"
74
Transient V receptor-1 (TVR1)/ Vanilloid/ Capcasin
when it is open....
K out
Na, Ca in
similar to NMDA
75
Increasing K conductance means...
more K flows OUT
76
Bradykinin is considered a..
inflammatory mediator
77
increasing Bradykinin results in
increased DAG & IP3
increases overall response of system
78
T/F
CNS neurons can be sensitized for pain transmission by many inflammatory mediators
False
peripheral
79
released in response to tissue damage
bradykinin
80
Chronic pain occurs when
inflammatory effects do not resolve
leading to hyperalgesia due to sensitization
81
T/F
Hyperalgesia is a result from nerve understimulation.
False
hyperalgesia is due to sensitization/*over*stimulation
82
Allodynia
perception of pain from normally non-painful stimuli
body's response to sensitization
83
T/F
Allodynia can occur without a stimuli
False
It is specifically pain from a nonpainful stimuli
84
Where is adenosine released from?
damaged tissue
85
Pain inhibitory receptors
Mu (endorphins)
GABA A
M2 (ACh)
GIRK
SSTR2a
86
Endorphins act on ____ receptors
Mu
87
Which propagate pain? Which are inhibitory?
NMDA
GABA
AMPA
propagate: NMDA & AMPA
inhibit: GABA
88
Substance P
MoA
act on NK1 > G Prtn > cAMP & PKA >VR1/NMDA (increases + [ ]/depolarization)
89
Glutamate MoA
act on AMPA
Na in
depolarization/pain nociception
90
GABA MoA (pain)
increases Cl- conductance
hyper polarizes
signal harder to propagate
91
Dorsal Horn Synapse
**Afferent** substances
SP
glutamate
92
White and grey matter
SC vs brain
SC: grey inside; white outside
brain: grey outside; white inside
93
White matter vs grey matter
whats in it?
White matter: myelinated axons; pathways/tracts
Grey matter: cell bodies/cellular region
94
Stimulation of ___ ___ causes the anger a/w pain
insular cortex
95
Amygdala transmit signals to
insular cortex
96
Lower level pain structures
Rostral ventral medulla
Periaqueductal Gray (PAG)
-respiration
-BP
-emotion
-lizards
97
insular cortex
brings into consciousness
specifically conscious emotion
ie: anger
98
T/F
nociceptors synapse once at the spinal cord
False
can have 1 or more
99
The thalamus relays info to
somatosensory cortex
100
T/F
In the brain, most pathways are outside and transmit to cells in the inner region.
False
most brain pathways are INSIDE
&
transmit to cells the outer regions
101
Where do nociceptors enter the spinal cord?
Dorsal spinal column
102
functions as a relay center for nociceptive and other sensory activity
spinal dorsal horn
103
periaqueductal gray (PAG)-RVM (rostral ventromedial medulla) system may either depress or facilitate the integration of painful information in the ______
spinal dorsal horn
104
Primary afferent nociceptors convey noxious information to
projection neurons within the dorsal horn (SC)
105
make up the great majority of the neuronal population throughout the dorsal horn
interneurons
106
Ascending pathway
107
Ascending information also accesses neurons of the ___ and ___ to engage descending feedback systems that regulate the output from the spinal cord.
rostral ventromedial medulla (RVM)
midbrain periaqueductal gray (PAG)
108
T/F
Cell bodies are usually found in the dorsal horn.
false
dorsal root
109
Which fibers enter thru the dorsal root?
AB, Ad, C
110
Dorsal root fibers & their laminae
111
Processing neurons
augment or inhibit depending on...
the level the information comes in on
112
Gate Theory of Pain
Pain information is transmitted to the brain if the gate is open but not if the gate is closed by inhibitory stimulation
113
Explains how fibers can augment/modulate pain
Gate Theory of Pain
114
T/F
A neuron must synapse on another neuron's terminal to inhibit the passage of pain signals.
False
does not have to synapse only here
115
The mechanism of rubbing skin when in pain
activates large myelinated afferents (Aβ) (“faster” than Aδ & C fibers that convey pain)
Aβ fibers deliver pressure & touch info to dorsal horn
↓
overrides some pain messages (Aδ & C fibers) by **activating the inhibitory interneurons in the dorsal horn**.
116
T/F
Rubbing skin stimulates additional mechanical inputs which inhibit the gate through A-delta fibers and diminishes pain transmission to the brain
False
inhibit the gate through Aβ fibers
rubbing activates large myelinated afferents (Aβ) (“faster” than Aδ & C fibers that convey pain)
Aβ fibers deliver pressure & touch info to dorsal horn
↓
overrides some pain messages (Aδ & C fibers) by activating the inhibitory interneurons in the dorsal horn.
117
Which fibers tend to be stimulating? Which are inhibitory?
Adelta
C
AB
Stimulating: Ad & C (small)
inhibiting: AB (large)
118
The gate is seen as an (excitatory/inhibitory) mechanism
inhibitory
119
How does a very strong pain stimulus affect Ad & C fiber modulation?
High degrees of pain can enhance the stimulating effect of Ad & C fibers
-block Ab fibers
-enhance pain by inhibiting the closing of the gate
esp if many fibers are affected
120
The neurologic “gate” is in....
the spinal dorsal horn
121
GCT
painful information is projected to the ____ brain regions if the gate is open, although painful stimulus is not felt if the gate is closed by….
supraspinal
simultaneous inhibitory impulses (ie: rubbing skin)
122
large-diameter myelinated afferent fibers
AB
123
How we harvest Opium
-Slice poppies open
-Collect dried resin (morphine & other natural opioids)
-Modify via chemical treatment to make diff compounds (semi-synthetics; heroin)
124
Opium first known use
100 AD rome
125
alkaloids
naturally occurring compound in plants
126
Codeine and Papaverine and examples of
alkaloids (naturally occurring compounds in plants)
127
Morphine chemically isolated in
1806
128
Papaverine
no pain relief activity
activity on GIT
TB: papverine & noscapine lack analgesic activity
129
Does codeine relieve pain?
Yes, but not as potent as morphine.
130
Meperidine is an example of...
Synthetic congeners
(fully synthetic)
131
T/F
Heroin is a synthetic product of morphine.
False
semi-synthetic
132
How we make semi-synthetic opioids
-Collect dried resin (morphine & natural opioids)
-chemical treatment to make diff compounds = semi-synthetic
ie: heroin
133
T/F
Opiates refers to all agents acting on morphine receptors, including antagonists.
False
Opiates = derived from opium
Opioids: all agents acting on morphine receptors, including antagonists
134
T/F
All opioids have pain-relieving properties.
False
Opioids = *all* agents acting on morphine receptors, including antagonists.
135
T/F
Stupor specifically refers to opioids.
False
anything that produces stupor in theory could be considered a narcotic
136
Opioid Receptors
major families
m, d, k, Nociceptin
"Four"
137
Four major families (m, d, k, Nociceptin) all belong to ....
the G protein-coupled class of receptors.
138
Endogenous ligands for opioid receptors are ___ with ___ for each receptor type
peptides
varying affinities
139
T/F
All opioid receptor activity is inhibitory
False
very low doses are actually excitatory (increases intracellular cAMP)
140
Opioids exhibit inhibitory activity by...
decreasing adenylate cyclase
↓
decreases intracellular cAMP
141
T/F
Excitatory responses to opioids can be seen with clinical doses.
False
this is seen in a testing/lab environment; usually not seen in pts
142
converts ATP to cAMP
adenylate cyclase
(Adenylyl cyclase = adenylate cyclase)
143
Which are excitatory?
Which are inhibitory?
Go
Gi
Gs
excite: G**s**
inhibit: Gi Go
"**s**timulate”
G**i** = **inhibit**
144
Ca and K conductance that will increase action potential
Decrease K cndxn
Increase Ca cndxn
“Keep my K. Ca, come in!”
145
T/F
Opioid Receptors are found all over the body.
true
146
Opioid Receptor Locations:
mu, kappa, delta
Mu: brainstem & thalamus; some SC; GIT
K: dorsal H; some Bstem medullary retic.
d: limbic
147
Which opioid receptors are mainly a/w lower level fxns?
Kappa
Delta (lower lvl consciousness & emotion)
“My K:D is a lower level”
148
Opioid Receptor Functions
Mu
analgesia
**resp depression
euphoria
miosis
physical dependence**
decreased GI motility
Mu = euphoria "Muphoria"
149
physical dependence
overstimulation = tolerance
body craves more to stimulate same pathway
150
Mu receptor [ ] is highest in...
the GIT
151
T/F
physical dependence is the reason for opioid abuse
False
euphoria leads to abuse
152
Opioid Receptor Functions
Kappa
supraspinal analgesia
sedation
dysphoria (psychoses)
153
Opioid Receptor Functions
Delta
analgesia (spinal?)
D Does 1 thing = analgesia
154
a/w recovery effects in **long term addicts** (craving/dependence)
Kappa receptor dysphoria (psychoses)
155
Endogenous Opioids are derived from
precursor polypeptides
156
Endogenous Opioids
agents
endorphins
dynorphins
enkephalins
157
Endogenous Opioids
All differ in ____, but share the same ...
chain length
first few AA’s (61-65)
158
smallest unit that produces response at opioid receptors
Met-Enkephalin
(AA 61-65)
159
How we cleave to obtain the different endogenous opioids
B-endorphin (61-91)
y-endorphin (61-77)
A-endorphin (61-76)
Met-Enkephalin (61-65)
160
ACTH & B-LPH
both: neurohumoral control
ACTH: control adrenaline release
not pain relieving!
161
Met-Enkephalin (61-65) is a ___ unit structure
5
smallest unit that produces response at opioid receptors
162
Endomorphines
newly discovered mu-receptor selective **tetra**peptides
163
T/F
Endomorphines come from the same peptide structure as the endorphins, dynorphins, and enkephalins.
False
164
Endomorphines role in pain
Act as NTs, neuromodulators, or neurohormones
decrease signal strength or block completely)
Body’s pain modulators
165
Opioid Receptor Homology
~65% homology exists among m, d, k
Open circles are AA’s that differ among each receptor type.
166
T/F
The opioid G receptor proteins are more similar in terms of their ligands rather than how they work.
False
more homologous in terms of intracellular side, which controls how it works
external portion (binding site) is less homologous
167
Analgesia mediated via receptors located in...
-dorsal horn (SC)
-periaqueductal gray matter
-thalamus
168
PAG process information & brings it to ___ levels of the brain.
The thalamus, brings info to ___ levels.
PAG → lower levels
thalamus → higher levels
169
Ventral brainstem receptors mediate effects on...
coughing
vomiting
respiration
pupillary diameter
170
Can create substances to augment pain
hypothalamus
171
Neuroendocrine functions controlled via the ___.
hypothalamus
172
amygdala is a/w
Mood and behavioral effects
173
associated mainly with the GI tract
Peripheral mu receptors
174
Opioid ligands can interact with opioid receptors in 4 primary ways:
-agonist (can be inhibitory!)
-antagonist
-partial agonist
-Mixed agonist/antagonist
175
T/F
An opioid agonist can inhibit the opioid receptor.
True
Agonist: binds & activates receptor.
Agonists CAN be INHIBITORY
"can be inhibitory in its agonist activity"
176
binds to the receptor but does not activate it
antagonist
177
Partial Agonist
-binds but produces a submaximal response
-**Lacks intrinsic activity**
178
Mixed Agonist/Antagonist
binds to more than 1 type of opioid receptor
acting as an agonist at one, and an antagonist at others
179
Stimulating a G protein receptor typically leads to a ___ action
inhibitory
180
T/F
If we give higher doses of a partial agonist/antagonist, it is possible to achieve maximal effect.
False
partial agonist/antagonist lacks intrinsic activity
181
Opioids are (bases/acids) and bind to receptors in (ionized/nonionized) form.
opioids = bases & bind in ionized form
ionized form = + charge
(bases accept protons)
182
Opioid MoA
CNS activity primarily in...
brainstem/spinal cord
183
Opioid MoA
Non-CNS activity
peripheral afferent neurons
184
Opioids
Primary action
decreased neurotransmission by **presynaptic** inhibition of neurotransmitter release (NE, ACh, DA, SubP)
↓
increased potassium conductance and/or calcium channel inactivation
185
Opioid action is (mostly/all/rarely) pre-synaptic.
mostly pre-synaptic
some post-synaptic inhibition
186
Central Opioid Effects
↓ Neuronal activity
Analgesia – ↑ perception threshold & tolerance
Resp dprsn – ↓ CO2 sensitivity (Cheyne-Stokes)
Mood – clouded state (agonists); euphoria
Sedation – agonist dependent
Miosis
N/V
antitussive
endocrine
187
Opioids
Endocrine effects MoA
inhibits LHRH secretion
188
Cheyne-Stokes resp
rapid RR, apnea, repeat
not sensing CO2 during apnea
CO2 builds up to a higher extent triggers rapid RR
CO2 drops
apnea restarts
189
Peripheral Opioid Effects
Histamine release – peripheral arteriole & venous dilatation
Venous dilatation – direct opioid receptor action.
Smooth muscle contraction – biliary and bladder sphincter muscles. (↓ bile & urine)
Inhibit ACh release – mesentery: constipation.
190
Codeine has (high/low) Mu activity.
low
191
Histamine release w/ opioids
innate response
can occur on the first dose
Don’t give large doses without resp support
192
Opioids constipation MoA
Inhibition of ACh release in mesentery
↓
decreases peristalsis
↓
constipation
193
T/F
constipation can cause infection
True
bacteria can multiply & move up intestines
30-50% fecal matter = bacteria
194
opioids + ___ ___ = worsened constipation
bowel manipulation/surgery
195
Therapeutic Opioid Uses
Analgesia – acute & chronic
Pre-op sedation, anesthesia, epidural analgesia.
Diarrhea (Lomotil)
Cough suppression(codeine)
Opioid withdrawal
Opioid overdose (antagonist)
*Remember opioids can be antagonists too*
196
Why do we give opioid w/drawl pts more opioids?
Trying to block internal response (N/V)
give opioid w/ more targeted action
197
"MOR"
Mu opioid receptor complex
198
MORs can be found (2)
PAG
Dorsal horn (SC)
199
Opiate analgesia pathway
Start → finish
Medulla
dorsal raphe
PAG
Locus coeruleus
spinal cord
200
MOR PAG Opiate action
MOR activation = Inhibits GABA release
↓
PAG outflow & signal passage
↓
activates forebrain, spinal & monoamine rcptrs
↓
input to higher centers & mood
201
MOR Spinal Opiate Action
second order dorsal horn:
Pre & Post synaptic MOR
Pre: block Ca
Post: ↑K cndxn (hyperpolarize)
Result: hyperpolarize POST synaptic membrane
202
_____ MOR are a/w K+ & Ca++ channels
Spinal/2nd order DH
203
Opiate receptor binding is highly expressed in the
superficial spinal dorsal horn (substantia gelatinosa)
presynaptic C fibers (small aff)
204
Opiate agonist acting @ spinal sites serves to...
Lessen afferent excitation of the second order neuron
205
small primary afferent fibers
C fibers
"C small af"
