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NEUR 350 > Pain > Flashcards

Pain Flashcards

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1
Q

What is pain?

A

an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage

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2
Q

What are the two components of pain?

A

sensory-discriminative
affective-motivational

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3
Q

What is the sensory-discriminative aspect of pain?

A

the noxious stimulations location, intensity, and quality

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4
Q

What is the affective-motivational aspect of pain?

A

the unpleasant feeling, the fear and anxiety, and the autonomic activation that accompany expoure to a noxious stimulation
*behavioural

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5
Q

What are the brain areas associated with sensory components of pain?

A

primary somatosensory cortex
secondary somatosensory cortex
posterior insula

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6
Q

What are the brain areas associated with affective components of pain?

A

dorsal anterior cingulate cortex
anterior insula

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7
Q

How can hypnosis affect pain?

A

might alleviate pain by decreasing the activity of brain areas involved in the experience of suffering (affective)

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8
Q

What occurred to sensory brain areas when hypnotic suggestion was used?

A

the activity of the somatosensory cortext did not change with or without hypnotic suggestions

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9
Q

What occurred to affective brain areas when hypnotic suggestion was used?

A

the anterior cingulate cortex was much less active when subjects were told pain would be minimally unpleasant

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10
Q

What is asymbolia?

A

patients with lesions in the anterior cingulate or insular cortex percive noxious stimuli as painful and can distinguish sharp from dull pain and identity location and intensity aspects
but they fail to display the appropriate emotional response (not bothered or suffering from it)

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11
Q

Why might patients giggle in response to pain?

A

they can still sense the pain (danger) but the pain is no longer aversive (false alarm)

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12
Q

What is social pain?

A

the unpleasant experience that is associated with actual or potential damage to ones sense of social connection or social value (owing to social rejection, exclusion, negative evaluation, or loss)

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13
Q

What brainr egions are activated during soical rejection?

A

affective pain regions (dorsal anterior cingulate cortex and anterior insula)
as well as self reported distress was high in states of social rejection

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14
Q

What is the affect of tylenol on social rejection?

A

people taking tylenol before experiencing social rejection reported less distress than those taking a placebo
as well as less activation in affective pain regions of the brain

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15
Q

What is nociception?

A

the sensory processes of encoding and processing noxious stimuli, depends on specifically dedicated receptors and pathways distinct from the sensory processing of ordinary mechanical stimulation

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16
Q

What is a nociceptor?

A

the unspecialized free nerve cell endings that responds to stimuli that produce tissue damage or pose the threat of damage and initiates the sensation of pain

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17
Q

What are free nerve endings?

A

an axon that terminated in the skin without any specialized cell associated with it and that detects pain and/or changes in temperature

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18
Q

What is a receptor cell?

A

a specialized cell that responds to particular energy or subatnce in the internal or external environment and converts energy into a change in the electrical potential across its membrane

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19
Q

What are labeled lines?

A

the concept that each nerve input to the brain reports only a particular type off information

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20
Q

What is sensory transduction?

A

the process in which a receptor cell converts the energy in a stimulus into a chnag in the electrical potential across its membrane

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21
Q

What is a receptor potential?

A

also called generator potential
a local change in the resting potential of a receptor cell thate mediates between the impact of stimuli and the initiation of APs

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22
Q

What speed do pain fibers conduct at?

A

relatively slow speeds
due to light or no myelination on the axons
with light myelination slightly faster than without
*creates smaller diameter

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23
Q

What is the speed of AP a function of?

A

each fibers cross sectional diameter

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24
Q

What does the first and second pain being carried by two different primary afferent fibres create?

A

two differnt pain sensations
first (faster) - sharp short pain
second (slower) - dull long pain

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25
How is noxious stimuli transduced?
into electrical acitivity at the peripheral terminals of unmyleinated C-fibre and thinly mylinated A-fibre nociceptors by specific receptors or ion cahnnels sensitive to heat, mechanical stimuli, protons, and cold - then conducted to the spinal cord, central pathway, and cortex where pain sensation is experienced
26
How are TPR pathway channels opened?
Bradykinin binds to G protein coupled receptors on the surface of primary afferent neurons to activate phospholipase C, leading to the hydrolysis of PIP2 and production of IP3 -> release of Ca2+ from intracellular stores activation of protein kinase C regulates TPR channel activity, TRPV1 channel is sensitized leading to channel opening and Ca2+ influx
27
What do the free nerve endings with TRPM8, TRPV1, and TPRM3 response to?
TRPM8 - temperatures below normal body temp TRPV1 - moderate heat and capsaicin found in chili peppers TRPM3 - high temperatures
28
What speed do the free nerve endings with TRPM8, TRPV1, and TPRM3 transmit at?
TRPM8 TRPV1 - along slow unmyelinated C fibres TRPM3 - along fast large myelinated A fibres
29
How do the nerve cells with TRPM8, TRPV1, and TPRM3 vary with threshold?
TRPM3 - low TRPV1 - high TRPM8 - medium *create a different response to stimuli
30
What is coding?
the rules by which APs in a sesnory system reflect a physical stimulus
31
What is range fractionation?
a hypothesis of stimulus intesnity perception stating that a wide range of intensity values can be encoded by a group of cells, each of which is a specialist for a particular range of stimulus intensities
32
What is the TRPV1 receptor?
a receptor that binds capsaicin to transmit the burning sensation from chili peppers and normally detects increases in temperature
33
What is the TRPM3 receptor?
a receptor found in some nerve endings that opens its channel in response to rising temperature
34
What is the TRPM8 receptor?
a sensory receptor found in some free nerve endings that opens an ion channel in response to a mild temperature drop or exposure to menthol
35
What is the affect of peripheral sensitization?
The area of mechanical hyperalgesia is larger than the flare the mechanical threshold for pain is significantly decreased post injury
36
What are potential mediatiors fo peripheral sensitizaition?
Mast cells releasing mediators (histamine, bradykinin) macrophages releasing cytokines (bradykinin)
37
What is the effect of the mediators on peripheral sesitization?
may act direcly to alter the sensitvity of peripheral nociceptors or indirectly via coupling to one or more peripheral membrane bound receptors binding lignads to receptors can initial a cascade of events that includes activation of second messenger systems and alteration of gene regulation
38
Explain the mechanism of peripheral sensitization
with inflammation, components of the inflammatory soup (bradykinin or prostoglandins) bind to G protein coupled receptors and indue activation of protein kinases A and C in nociceptor peripheral terminals, which then phoshorylate ion channels and receptors results in the threshold of activation of the transducer receptor is reduced, and the excitability of peripheral terminal membrane increases, producing a state of heightened sensitivity
39
What is allodynia?
pain caused by a normally non-painful stimulus
40
What is hyperalgesia?
a heightened experience of pain caused by a noxious stimulus
41
What is hypoalgesia?
a decreased perception of pain caused by a noxious stimulus
42
What are the efferent actions of nociceptors?
a noxious stimuli will also lead to an AP that propagates efferently to peripheral branches they lead to release neuropeptides that can stimulated epidermal and immune cells, or lead to vasodilation, plasma extravasation, and smooth muscle contraction
43
What is the role of CGRP in neurogenic inflammation?
produces dilation of peripheral blood vessels resultant edema causes additional liberation of bradykinin
44
What is the role of substance P in neurogenic inflammation?
acts on mast cells to evoke degranulation and the release of histamine which direclty excites neurotransmitters it alos produced plasma extravasation
45
What are the four stages in neurotrophins as pain mediators?
1. peripheral exposure to NGF - binds to primary nociceptive terminals 2. retrograde transpot of signalling endosomes - increase excitability 3. increased transcription of BDNF - enhanced expression of BDNF 4. central reslease of BDNF - released from sensoru terminals and spinal cord
46
What is the role of pain specifc sodium channels?
NaV1.7 channel transform generator potentials from the pain signaling pathway into AP in the adjacent pacemaker zone transmitted slong the afferent sensory fibers
47
Explain how a grasshopper mouse does not feel pain from the bark scorpion venom
The bark scorpion toxin activates Na1.7 channels in grasshopper and lab mice in grasshopper mice the toxin protently inhibits the NaV1.8 channel in the same sensory neurons tipping the balance to inhibit AP firing in nociceptors
48
What fibers do neurons in lamina I of the dorsal horn receive input from?
direct - myelinated A nociceptor fibers direct & indirect - unmylinated C nociceptor fibres via interneurons on lamina II
49
What fibers do neurons in lamina V of the dorsal horn receive input from?
low threshold input from large diameter myelinated fibers A of mechanoreceptors from nociceptive afferent fibers A and C
50
Where does lamina V neurons send dentrites to?
lamina IV where they are contacted by the terminals of AB primary afferents
51
Where do dendrites in lamina III go to?
arising from cells in lamina V are contacted by the axon terminals of lamina II interneurons
52
What is the neural basis of referred pain?
convergence of visceral and somatic afferent fibers nociceptive afferent fibers from the viscera and fibers from specific areas of the skin converge on the same projection neurons in the dorsal horn. The brain has no way of knowing the actual site of the noxious stimulus and mistakenly associates a signal from a visceral organ with an area of skin
53
What are the two classes of synapitc vessesl on the terminal of a C fibre on a dendrite and what do they contain?
small electron-lucent vesicles contain glutamate large dense-cored vesicles hold neuropeptides
54
Where are glutamade and the peptide substance P scattered?
in the axoplasm of a sensory terminal in lamina II of the dorsal horn
55
Where is substance P in the highest concentration?
in lamina I
56
How does pain ascend the spinothalamic system to reach the brain?
sensation of pain travels from its origin to the brain via the spinothalamic system crossing the midline in the spinal cord before ascending to the thalamus
57
What is the anterolateral system (spinothalamic system)?
a somatosensory system that carries most of the pain and temperature information from the body to the brain
58
What is the anterolateral pathway (spinothalamic)?
primary afferent axons terminate in dorsal horn -> SECONDARY AXONS CROSS MIDLINE -> ascend contralateral anteriolatereal column to thalamus *pain and temperature
59
What is the dorsal column pathway?
primary afferent axons enter spinal cord -> ascend the ipsilateral dorsal columns -> synapse in medulla -> SECONDARY AXONS CROSS MIDLINE -> ascend to contralateral thalams *mechanosensory
60
What is a hemicord lesion (brown-sequard syndrome)?
a lesion restricted to the left half of the spinal cord results in dissociated sensory loss and mechanosensory deficits on the left half of the body, wiht pain and temperature defecits on the right
61
What are the descending pathways?
sertonergic pathway noradrenergic system
62
What is the function of the descending pathways in the spinal cord?
inhibit nociceptive projection neurons through direct connections as well as through interneurson in the superficial layers of the dorsal horn both pathways recive input from neruons in the periaquaductal grey region
63
What do local enkephalin containing interneurons exert?
both pre and post synapic inhibitory actions at synapses
64
What do serotonergic and noradernergic neurons in the brainstem activate and suppress?
activate the local interneurons and suppress the activity of the spinothalamic projection neurons
65
What is naloxone?
a potent antagonist of opiates that is often administered to people who ahve taken drug overdoses it blocks receptors for endogenous opiods
66
What is analgesia?
absence of or reduction in pain
67
What are opiates?
a class of compound that exert an effect like that of opium, including reduced pain sensitivity
68
What are endorphins, enkephalins, and dynorphins?
three kinfs of endogenous opioids, substances that reduce pain perception
68
What are endogenous opioids?
a class of peptides produced in various regions of the brain that bind to opiod receptors and act like opiates
69
What is an opioid receptor?
a receptor that responds to endogenous and/or exogenous opioids
70
What is periaquaductal gray?
the neuronal body - rich region of the midbrain surrounding the cerebral aqueduct that connects the third and fourth ventricles involved in pain perception
71
What are the two ways of regulation of nociceptor dingals at dorsal synapse?
1. activation of nociceptor leads to the release of glutamate and neuropeptides from the primary sensory motor neuron, producing an excitatory postsynapic potential in the projection neuron 2. opiates decrease the duraction of the postsynaptic potential, probably by reducing Ca2+ influx and thus decreasing the release of transmitter from the primary sensory teminals - opiates hyperpolarize the dorsal horn neurons by activating a K+ conductance and this decrease the amplitude of the postsynaptic potential in the dorsal horn neuron
72
Where are the opioid receptors in the body?
brain brainstem spinal cord peripheral neurons intestine
73
What are peripherally restricted opioids?
molecules that don't cross the blood brain barrier
74
How does a new opiod target disease specific conformations?
by selectively activating opiod receptors where acific conditions prevail (tissues affected by inflammation or injury) *does not affect health tissue
75
What is the placebo effect?
a physiological response following the administration of a pharmacologically inert "remedy" - external and internal environment

NEUR 350 (11 decks)

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