Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

6BBYN302 Perspectives on Pain and Nervous System Disorders > Chemical anatomy of pain (1) > Flashcards

Chemical anatomy of pain (1) Flashcards

To discuss neurochemical variety of DRG neurons (particularly nociceptors); To highlight the progressive changes in our understanding of the characteristics of nociceptors, in relation to technical developments; To discuss the issue of the functional specificity of different identifiable subpopulations of nociceptors To draw attention to the areas of uncertainty/controversy in the field.

1
Q

How are innocuous stimuli transmitted in the somatosensory system?

A
  • through Abeta fibers and travel via the dorsal column medial lemniscus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How are noxious stimuli transmitted in the somatosensory system?

A
  • through C and Adelta fibers and travel via spinothalamic tract
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How does the somatosensory system process sensory information, especially in the context of pain?

A
  • somatosensory system comprises parallel pathways (for processing various sensory info e.g. touch, pain, temp)
  • convergence of pathways can occur, where different types of sensory info are integrated & processed together
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the primary role of the dorsal root ganglia (DRG) in the somatosensory system?

A
  • acts as a cluster of sensory nerve cell bodies that transmit sensory info from periphery to CNS
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What type of neurons are found in the DRG?

A
  • DRG contains pseudo-unipolar sensory neurons, which have a single process extending from the cell body that bifurcates into both peripheral and central branches
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the first step in somatosensory processing, and where does it occur?

A
  • first step is transduction, (takes place in periphery) where DRG neurons convert various sensory stimuli into electrical signals
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What happens after transduction in somatosensory processing?

A

sensory signals are transmitted to CNS via the central branch of DRG neurons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What part of the central nervous system processes and interprets somatosensory information?

A
  • cerebral cortex is responsible for the perception and interpretation of somatosensory input
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the role of DRG neurons in modulation within the somatosensory system?

A
  • involved in the modulation of sensory information, influencing how we perceive sensations like pain
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the fundamental processes involved in sensation within the somatosensory system?

A
  • Sensation involves transduction of stimuli from the periphery
  • DRG neurons play a role in this process
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe the steps of sensory signal processing in the somatosensory system

A
  • Transmitted signals are sent to CNS
  • Perception occurs in the cerebral cortex, enabling conscious awareness of the sensory input
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How can the perception of sensation, especially pain, be modulated within the somatosensory system?

A
  • Modulation processes can change how sensations perceived - incl. pain
  • Sensory neurons use neurotransmitters like glutamate (NMDA/AMPA/mGluR) for signal transmission.
  • Neuromodulators like substance P, acting via NK1 receptors, can influence sensory processing
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the characteristics of cutaneous nociceptors in terms of localization and sensations?
Back:

A
  • well-localized
  • can produce sensations like pricking, stabbing, and burning
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How do muscle and visceral nociceptors differ from cutaneous nociceptors in terms of localization and sensations?

A
  • Muscle & visceral nociceptors are much more poorly localized
  • can generate sensations such as aching, cramping, fullness, dullness & vagueness
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What contributes to the differences in localization and sensation between cutaneous and visceral nociceptors?

A
  • influenced by the distribution of C-fiber components in the skin compared to visceral afferents & their connections to central and peripheral terminals
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Where do the peripheral processes of dorsal root ganglion (DRG) neurons innervate receptors?

A
  • the skin, muscle, and viscera
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How can the peripheral processes of some DRG cells influence vascular activity?

A
  • Some DRG cells’ peripheral processes release vasoactive mediators that change vascular permeability, indicating efferent as well as afferent activity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are A fibers, and what types of input do they process?

A
  • sensory nerve fibers with low threshold input sensitivity, primarily processing mechanosensation
  • they’re myelinated & conduct signals rapidly
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are C fibers, and what types of input do they process?

A
  • sensory nerve fibers with high-threshold sensitivity, processing mechanical, thermal, and chemical (polymodal) stimuli
  • they’re unmyelinated & have slower conduction velocities
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the two main subgroups of C fibers?

A
  • peptide-rich
  • peptide-poor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What neuropeptides are released by C fibers in the periphery, and what are their functions?

A
  • C fibers (particularly peptide-rich subpopulation) release substances such as substance P and CGRP in the periphery
  • these neuropeptides have vasoactive properties & can promote inflammatory responses
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How were polymodal nociceptors initially proposed to be divided into two groups?

A
  • suggested to be divided into 2 groups based on their content of peptide and fluoride-resistant acid phosphatase (FRAP)
  • as well as their termination sites within the spinal cord
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Majority of C-fibers are what?

A
  • polymodal & responds to all
    forms of noxious stimuli (thermal, mechanical and chemical)
  • with varying degrees of sensitivity
23
Q

Is there any overlap between Aβ fibers and nociceptors? If so, what type of pain do they typically transmit?

A

-Yes, there is some overlap
- Aβ fibers can transmit mechanical, prickling, fast pain that is often localized

24
Q

What happens to C fiber classes (peptidergic and non-peptidergic) as they develop, and how do they differ in terms of neurotrophic support requirements?

A
  • C fiber classes (peptidergic and non-peptidergic) diverge during development
  • Non-peptidergic fibers become responsive to glial cell-derived growth factors, and this responsiveness is influenced by target tissues.
25
Q

What is the role of Nerve Growth Factor (NGF) in relation to nociceptors?

A
  • NGF levels increase in inflamed tissues
  • and it plays a significant role in nociceptor sensitization and pain modulation
26
Q

What are the major DRG subgroups based on their trophic factor response?

A
  • A fibers, C fibers (divided into peptide-rich and peptide-poor)
  • each of which responds to specific trophic factors for development and survival
27
Q

What is the characteristic response of peptide-poor C fibers?

A
  • Peptide-poor C fibers preferentially respond to ATP, contributing to their nociceptive function
28
Q

What is a common neurotransmitter among these different DRG subgroups, and how do they differ in terms of transporters?

A
  • Glutamate is a common neurotransmitter in these subgroups
  • they use different transporters for glutamate uptake, which can influence their synaptic functions
29
Q

How are C fibers divided into two groups based on their characteristics?

A

one group:
- expressing receptors for GDNF
- terminating in the deeper parts of the substantia gelatinosa (laminae 2) of the spinal cord

other group:
- synthesizing peptides like substance P,
- expressing NGF receptor TrkA
- terminating more superficially in the dorsal horn

30
Q

How can neurons in the ascending nociceptive pathway change their phenotype in response to sustained peripheral injury?

A
  • Neurons in the ascending nociceptive pathway can change their phenotype in response to sustained peripheral injury
  • leading to new gene expression in the spinal cord and brain
  • resulting in a new pattern of gene expression that changes substantially over time
31
Q

What ion channels are involved in nociceptor function?

A
  • Nociceptors involve various ion channels, including:
  • Transient Receptor Potential (TRP) family for detecting a wide temperature range.
  • TRP channels predominantly expressed in nociceptors & associated with tissue injury & inflammation.
  • e.g. TRPV1 is upregulated in inflammatory conditions
32
Q

What are the roles of Acid-Sensing Ion Channels (ASIC) in nociceptors?

A

-play a significant role in pain and inflammation
- activated when extracellular pH decreases & are responsible for gating nociceptors

33
Q

Which ion channel is crucial for rapidly adapting mechanically activated currents in nociceptors, particularly in Merkel cells?

A
  • Piezo2 ion channels = vital for rapidly adapting mechanically activated currents in nociceptors, with a specific role in Merkel cells - associated with fine touch sensation.
34
Q

What role does the mass-related G protein-coupled receptor family play in nociceptors?

A
  • mass-related G protein-coupled receptor family is less understood, but used as a marker to differentiate non-peptidergic C fibers into groups
  • this differentiation allows for genetic modifications to study the loss of specific sensory sensations
35
Q

Which sodium channels are involved in nociceptor function?

A
  • Nociceptors utilize sodium channels, including Nav1.9 and Nav1.8, in their signal transmission
  • these channels are important for nociceptive processes
36
Q

What is the role of MrgprD in nociceptive neurons?

A
  • MrgprD = marker for non-peptidergic nociceptive neurons, representing approximately 75% of IB4-expressing neurons
  • exclusively innervate the skin & terminate in lamina II of the dorsal spinal cord
  • MrgprD neurons mainly function in mechanical nociception, indicating specificity in their sensory functions
37
Q

How does genetic ablation of C fibers expressing MrgprD affect sensitivity to different noxious stimuli?

A
  • genetic ablation of C fibers expressing MrgprD reduces behavioral sensitivity to noxious mechanical stimuli while leaving heat or cold sensitivity unaffected
  • suggests that brain distinguishes between different noxious stimulus modalities early in sensory processing
38
Q

What happens when TRPV1 nociceptors are selectively ablated?

A
  • abolishes sensitivity to noxious heat pain
  • but their elimination, when combined with ablation of MrgprD-expressing C fibers, results in an additive phenotype, indicating the brain’s early differentiation of various noxious stimulus modalities
39
Q

What anatomical differences suggest unique sensory functions for MrgprD neurons?

A
  • MrgprD neurons innervate the most superficial layers of the skin’s epidermis, specifically the Stratum granulosum
  • peptidergic CGRP neurons innervate the underlying Stratum spinosum.

These anatomical distinctions indicate that MrgprD neurons may have unique sensory functions.

40
Q

How do MrgprD neurons contribute to mechanical and thermal nociception?

A
  • they’re essential for full expression of mechanical nociception (but don’t play significant role in thermal nociception)
  • specific post-synaptic targets in the spinal cord’s lamina II (substantia gelatinosa) with which MrgprD neurons synapse remain unknown
41
Q

What is the method used to study MrgprD neurons’ function?

A
  • a method involved genetically targeting the light-activated ion channel ChR2-venus to the MrgprD locus.
  • these afferents terminate in laminae II of the spinal cord, suggesting their innervation of substantia gelatinosa (SG) neurons
  • this approach allowed precise control of a subset of nociceptors
42
Q

What did the study by Cavanaugh et al. in 2009 reveal about ChR2-venus expression?

A

-study by Cavanaugh et al. in 2009 found that ChR2-venus was expressed in non-peptidergic MrgprD DRG neurons
- indicating their involvement in optogenetic control of nociceptor activity

43
Q

How do MrgprD neurons contribute to responses to extreme cold and heat?

A
  • Pogorzala et al.’s 2013 study demonstrated that MrgprD neurons contribute to painful responses to extreme cold & heat.
  • While eliminating MrgprD neurons alone doesn’t affect behavioural responses to temperature, when combined with the ablation of TRPV1/8 cells, it significantly ↓ responses to extreme heat and cold
44
Q

What is the proposed role of Mrgprd C-11?

A
  • Mrgprd C-11 is thought to be involved in anti-nociception upon ligand binding
45
Q

How does TRPM8 knockout (KO) affect temperature sensitivity in mice?

A
  • In mice, the knockout of TRPM8 C fibres, associated with cooling sensation, results in an inability to discern temperature differences until they become noxious
46
Q

What happens when TRPV1 is knocked out in adult rats?

A
  • In adult rats, knocking out TRPV1 causes them to sit in noxious heat without realizing it
  • They still maintain cooling sensitivity.
47
Q

What is the function of the Merkel cell-neurite complex in the skin?

A
  • serves as a gentle touch receptor in the skin, mediating slowly adapting responses of Aβ sensory fibers to encode fine details of objects
48
Q

How does Piezo2 affect Merkel cells’ mechanosensitivity?

A
  • Merkel cells’ mechanosensitivity is completely dependent on Piezo2
  • Engineered mice deficient in Piezo2 in the skin show moderately ↓ behavioural responses to gentle touch
49
Q

What are the key conclusions regarding nociceptors and sensory processing?

A
  • A fibers and C fibers are morphologically, physiologically, and neurochemically distinct, supporting the idea of parallel sensory processing
50
Q

How many populations of nociceptors are there? and what are they?

A

3
- Ad/b HTM nociceptors (A-delta and C-fibers associated with high-threshold mechanoreceptors for fast pain).
- C-fibers comprising peptide-rich subpopulations.
- C-fibers comprising peptide-poor subpopulations.

51
Q

What is the role of Ad/b HTM nociceptors?

NOTE; Ad/b HTM = Ad and C-fibers (b) that are associated with high-threshold mechanoreceptors (HTM)

A
  • Ad/b HTM nociceptors are associated with fast pain transmission
52
Q

What are the two subpopulations of C fibers in the context of peptide content?

A
  • C fibers can be divided into peptide-rich & peptide-poor subpopulations
53
Q

How does the complexity of sensory integration affect perception?

A
  • it reflects the intricacies of perception & leads to various structure-function relationships between afferent phenotypes & target tissues
54
Q
A

6BBYN302 Perspectives on Pain and Nervous System Disorders (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions