Pain - The Basics Flashcards by Bryony Hawkins

Name four general peripheral structures which are innervated by nociceptive free nerve endings. (4)

Skin
Joints
Muscles
Viscera

How well did you know this?

Not at all

Perfectly

Describe the difference between the action potential profile produced in nociceptive neurones and non-nociceptive neurones. (1)

No difference

How well did you know this?

Not at all

Perfectly

Describe what is meant by ‘transduction of a stimulus’. (1)

Conversion of a peripheral stimulus (eg pressure) into electrical activity in a neurone.

How well did you know this?

Not at all

Perfectly

True or false? Explain your answer if appropriate. (1)

Action potentials produced in nociceptive neurones all have their peaks at the same membrane potential.

True - this is because action potentials are all or none

How well did you know this?

Not at all

Perfectly

Describe what is meant if a receptor potential is described as ‘subthreshold’. (1)

The depolarisation does not meet the membrane potential required to produce an action potential.

How well did you know this?

Not at all

Perfectly

What is meant by a ‘receptor potential’? (3)

A depolarising electrical signal

that occurs in a sensory receptor cell

when it is activated by an external stimulus.

How well did you know this?

Not at all

Perfectly

Explain why we can refer to a receptor potential as a ‘sustained depolarisation’. (2)

The membrane potential does not repolarise to resting between action potentials - it repolarises to the receptor potential.

The depolarisation does not tend to adapt as long as the stimulus is present so the cell will stay depolarised.

How well did you know this?

Not at all

Perfectly

Describe the relationship between the stimulus strength and the receptor potential. (2)

Rapid increase in receptor potential with increasing stimulus strength

when then reaches a plateau (no further RP increase with increased stimulus strength).

How well did you know this?

Not at all

Perfectly

Describe the relationship between the receptor potential and the frequency of action potentials produced. (1)

Directly proportional (higher RP = more APs)

How well did you know this?

Not at all

Perfectly

Very briefly describe how stimulus intensity (ie increased pain or touch) is conveyed in the nervous system. (1)

Increased frequency of action potentials = increased stimulus intensity

How well did you know this?

Not at all

Perfectly

Briefly suggest four ways that C and A fibre nociceptors can be distinguished. (4)

Cell body size
Fibre conduction velocity
Molecular markers
Electrophysiological and response properties

How well did you know this?

Not at all

Perfectly

Fill the gap relating to nociceptors and sensory neurones. (1)

Slowly conducting afferents tend to have …………………. cell bodies.

smaller

How well did you know this?

Not at all

Perfectly

Describe the issue with identifying nociceptors by their small cell bodies. (3)

Small cell body means that the fibre is a slowly conducting afferent fibre

however not all slowly conducting afferents are nociceptive

so small cell does not always equal nociceptive.

How well did you know this?

Not at all

Perfectly

True or false? Explain your answer if necessary. (1)

All C fibre sensory neurones are nociceptive, so all small cell bodies in the DRG will belong to nociceptive neurones.

False - a high proportion of C fibre neurones are nociceptive, so a high proportion of small DRG neurones will be nociceptive, but not all

How well did you know this?

Not at all

Perfectly

Describe how a compound action potential is obtained/measured. (3)

A whole nerve (not individual fibres)

is stimulated in one place

and CAP is recorded at a different place.

How well did you know this?

Not at all

Perfectly

Describe the number and ‘distribution’ of the peaks you would expect to see in a compound action potential of a sensory nerve. (2)

4 peaks

3 quick peaks quite close together, 1 peak a little while after

How well did you know this?

Not at all

Perfectly

Describe the reasoning behind the number and distribution of peaks seen in the compound action potential of a sensory nerve. (2)

3 quick peaks from Aa, Ab, and Ad fibres respectively

followed by a delayed peak from C fibres.

How well did you know this?

Not at all

Perfectly

Describe the diameter, myelination, and conduction velocity of Aa sensory fibres. (3)

Large diameter

Thickly myelinated

Fast conduction velocity

How well did you know this?

Not at all

Perfectly

Describe the diameter, myelination, and conduction velocity of Ab sensory fibres. (3)

Second largest diameter

Thickly myelinated

Second fastest conduction velocity

How well did you know this?

Not at all

Perfectly

Describe the diameter, myelination, and conduction velocity of Ad sensory fibres. (3)

Third largest diameter

Myelinated

Third fastest conduction velocity

How well did you know this?

Not at all

Perfectly

Describe the diameter, myelination, and conduction velocity of C sensory fibres. (3)

Thin diameter

Unmyelinated

Slow conduction velocity

How well did you know this?

Not at all

Perfectly

Name two structures innervated by Aa sensory fibres and describe their role. (3)

Muscle spindle

Golgi tendon organs

Muscle and joint proprioception

How well did you know this?

Not at all

Perfectly

Are Aa fibres nociceptive or non-nociceptive? (1)

Non-nociceptive

How well did you know this?

Not at all

Perfectly

Give an alternative name for Aa fibres, sometimes used when referring to fibres innervating muscle and joints. (1)

Type 1a and type 1b fibres

How well did you know this?

Not at all

Perfectly

Are Ab fibres nociceptive or non-nociceptive? (1)

Tend to be non-nociceptive

Give an alternative name for Ab fibres, sometimes used when referring to fibres innervating muscle and joints. (1)

Type II fibres

Are Ad fibres nociceptive or non-nociceptive? (1)

Can be either

Give an alternative name for Ad fibres, sometimes used when referring to fibres innervating muscle and joints. (1)

Type III fibres

Are C fibres nociceptive or non-nociceptive? (1)

Tend to be nociceptive

Give an alternative name for C fibres, sometimes used when referring to fibres innervating muscle and joints. (1)

Type IV

Name a molecular marker that could be used to identify myelinated nociceptors. (1)

NF200 (neurofilament)

Give two general categories of unmyelinated nociceptors that can be distinguished with molecular markers. (2) Name two molecular markers for each group that can distinguish them. (4)

Peptidergic (CGRP, substance P marker) Non-peptidergic (IB4, P2X receptor marker)

Apart from using the molecular markers CGRP and IB4, describe two other ways that peptidergic and non-peptidergic nociceptors can be distinguished. (2)

They respond to different growth/neurotrophic factors They express different receptors

Which of the following categories of nociceptor is the most common? (3) a) myelinated b) peptidergic c) non-peptidergic

b) peptidergic

Which nociceptor fibres (Ab, Ad, C) express substance P? (2)

- About 50% C nociceptors - A few Ab/d nociceptors

In which sensory nerve fibres (Aa, Ab, Ad, C) is CGRP expressed? (2)

Mostly A/C nociceptors Some A-LTM non-nociceptive fibres *LTM = low threshold mechanoreceptors

In which sensory nerve fibres (Aa, Ab, Ad, C) is Nav1.9 expressed? (1)

Only nociceptors (Ab/d and C)

In which sensory nerve fibres (nociceptors/low-threshold) is Nav1.8 expressed? (2)

Strong expression in nociceptors Weak expression in a few LTM *LTM = low threshold mechanoreceptors

In which sensory nerve fibres (Aa, Ab, Ad, C, nociceptors, low-threshold) is Nav1.7 expressed? (1)

Both nociceptors and non-nociceptors

In which sensory nerve fibres (Aa, Ab, Ad, C) is TrkA expressed? (1) What is TrkA? (1)

Only nociceptors (Ab/d and C) TrkA is a receptor for NGF

In which sensory nerve fibres (Aa, Ab, Ad, C) is IB4 expressed? (3)

Only C fibres which are nociceptive and non-peptidergic

In which sensory nerve fibres (Aa, Ab, Ad, C) is P2X3 expressed? (2) What is P2X3? (1)

On nociceptive C fibres which are IB4-positive. It is an ATP receptor.

In which sensory nerve fibres (Aa, Ab, Ad, C) are TRPV1/TRPA1 expressed? (2)

Nociceptive C fibres Both peptidergic and non-peptidergic populations

Describe both the thermal and mechanical thresholds for non-nociceptive Aa and Ab fibres. (2)

Thermal - none (unresponsive) Mechanical - Low

Give two sensory modalities that are conveyed by non-nociceptive Aa and Ab fibres. (2)

- Proprioception - Light touch

Describe Type I AMH fibres, in terms of Aa, Ab, or Ad fibres. (1)

Account for about a third of Ab fibres

Describe AMH nociceptors in terms of modalities and fibre type. (2)

Ab/d fibres which respond to mechanical and heat stimuli (polymodal)

Describe both the thermal and mechanical thresholds for nociceptive Type I AMH fibres. (2)

Thermal - High >53C Mechanical - Low

Describe the proposed role for nociceptive type I AMH fibres in both thermal and mechanical pain. (2)

Thermal - sensitisation Mechanical - first pain

Describe Type II AMH fibres, in terms of Aa, Ab, or Ad fibres. (1)

Account for all nociceptive Ad fibres

Describe both the thermal and mechanical thresholds for nociceptive Type II AMH fibres. (2)

Thermal - ~46C Mechanical - High

Describe the proposed role for nociceptive type II AMH fibres in both thermal and mechanical pain. (2)

Thermal - first pain Mechanical - may be silent or unresponsive

In general which nerve fibres (Aa, Ab, Ad, C) are responsible for 'first pain'? (1)

Ab/Ad

Give four sensory modalities that are transmitted by C fibres. (4)

- Nociception - Innocuous temperature - Itch - Pleasant touch (stroking)

Give eight separate types of C fibres (relating to modalities and thresholds). (8)

C-HTM C-heat C-cold C-polymodal C-unresponsive C-cool/warm C-pruriceptive C-LTM *HTM = high threshold mechanoreceptor *LTM = low threshold mechanoreceptor

Describe the threshold for both thermal and mechanical stimuli seen in C-HTM fibres. (2)

Thermal - High (~43C) Mechanical - High

Describe the threshold for thermal stimuli seen in C-heat fibres. (1)

High

Describe the threshold for thermal stimuli seen in C-cold fibres. (1)

Low (~6C)

Describe the threshold for both thermal and mechanical stimuli seen in C-polymodal fibres. (2)

Thermal - High Mechanical - High

Describe the threshold for both thermal and mechanical stimuli seen in C-unresponsive fibres. (2)

Thermal - no response Mechanical - no response

Describe the threshold for both thermal and mechanical stimuli seen in C-cool/warm fibres. (2)

Thermal - low Mechanical - no response

Describe the threshold for both thermal and mechanical stimuli seen in C-pruriceptive fibres. (2)

Thermal - no response Mechanical - no response

Describe the threshold for both thermal and mechanical stimuli seen in C-LTM fibres. (2)

Thermal - no response Mechanical - Low

In general which nerve fibres (Aa, Ab, Ad, C) are responsible for 'second pain'? (1)

C fibres

Name the general group of ion channels that act as thermoreceptors. (1)

TRP (transient receptor potential) channels

Name the subtypes of TRP channels, in a general order from detecting the hottest stimuli to the coldest stimuli. (9)

- TRPV2 - TRPV1 - TRPV4 - TRPM2 - TRPV3 - TRPM4 - TRPM5 - TRPM8 - TRPA1

Which TRP channel detects taste? (1) Give two particular tastes it can detect. (2)

TRPM5 - Soy sauce - Sugar

Which TRP channel acts as a mechanoreceptor in C nociceptors? (1)

TRPV4

Which TRP channel is located in keratinocytes and detects warm stimuli? (1)

TRPV3

Which TRP channel is known to detect noxious thermal stimuli in C fibres? (1)

TRPV1

Which TRP channel is suspected to be located in Type I AMH fibres? (1)

TRPV2

Which TRP channels are able to respond to cooling stimuli? (2)

TRPM8 TRPA1

Which TRP channel may be involved in nervous system sensitisation? (1) Suggest why this might be? (1)

TRPA1 It responds to a variety of natural chemical activators

Give three specific stimuli that TRPV1 may respond to. (3)

Chilli peppers Garlic Camphor

Give two specific stimuli that TRPM8 may respond to. (2)

Mint Eucaliptol

Give four 'food' stimuli that may activate TRPA1 channels. (4)

- Garlic - Mustard oil - Wasabi - Cannabinoids

Name two TRP channels that are activated endogenously by changes in pH and acidity. (2)

TRPV1 TRPA1

Describe the specific sensory modality carried by C-fibre low threshold mechanoreceptors. (1)

Gentle and pleasant touch

Describe the general threshold and adaptation properties of mechano-nociceptors and polymodal nociceptors. (2)

Threshold - tends to be high Adaptation - slowly adapting (response is maintained)

What is piezo? (1) How are they related to pain? (1)

Mechanotransducers/receptors They detect painful mechanical stimuli

Describe the adaptation properties of piezo1. (1)

Appears to be slowly adapting

Describe the adaptation properties of piezo2. (1)

Rapidly adapting

Name a location where piezo2 is abundant. (1)

Small and large DRG neurones

Describe the threshold properties of the piezo mechanotransducers. (1)

It is unknown whether they have high or low thresholds.

Give three general stimuli that are detected by the TRPA1 channel. (3)

- Cold - Pathological mechanical forces (injuries) - Natural chemical activators

Give 9 examples of natural chemical activators that can activate the TRPA1 channel. (9)

- pH - O2 - ROS (inflammation) - UVA light - NO - H2S - CO2 - Local and general anaesthetics - THC (cannabinoid)

Give two examples of mechanotransducers. (2)

- PIEZO2 - TRPA1

True or false? Explain your answer if necessary. (1) ASICs are mechanotransducers, and are important modulators in pathology.

False - ASICs are NOT mechanotransducers, however they ARE important modulators in pathology

Give the proper name for the ion channel group called ASICs. (1)

Acid-sensing ion channels

Name a stimulus that can activate ASICs. (1)

Low pH

Where do nociceptive neurones have their efferent functions? (1)

On small blood vessels

Give another name for the efferent effects of nociceptive neurones. (1) Explain this name. (1)

Axon reflex The effects can occur without contribution from the CNS

Give the general name for the efferent effect that nociceptive neurones have on blood vessels. (1) Name the general mechanism by which this effect occurs. (1)

Neurogenic inflammatory response Vasodilation

Name two molecules that are released by nociceptive neurones which mediate their efferent effects. (2)

Substance P CGRP

Name a cell type (apart from neurones) which are involved in the neurogenic inflammatory response. (1) Name two molecules released by this cell type. (2)

Mast cell - Histamine - Substance P

Name the three elements of the neurogenic inflammatory response. (3)

- Reddening - Flare - Wheal (oedema)

Give four normal physiological functions of the dorsal root ganglion (cell body) of the sensory neurone. (4)

- Control of neurotrophin expression - Calcium binding and store handling - Synthesis of transducers and neuropeptides, etc - Transport towards axon terminals

Give two normal physiological functions of the fibres (axons) of the sensory neurone. (2)

Insert ion channels and space them appropriately along the length of the fibre for action potential generation/conduction Ortho and anterograde transport

Give five normal physiological functions of the fibres (axons) terminals of the sensory neurone. (5)

- Feature multiple sites of transduction - Proximity of transduction to spike initiators - Modality specificity (due to transducer molecules) - Some local protein synthesis - Efferent function (peripheral release of SP/CGRP; neurogenic inflammation)

Describe the distribution of ion channels/transducers along the length of a sensory neurone. (1) Give a potential consequence of this. (1)

Spaced out all along the length of the nerve fibre. The neurone is vulnerable to activation all the way along the fibre (potential for neurogenic pain and sensitisation).

True or false? Explain your answer if necessary. (1) In sensory neurones, protein synthesis is only able to occur in the cell body, and proteins must then be transported along the axons.

False - there is also some local protein synthesis in peripheral terminals

Describe a benefit of local protein synthesis occurring in peripheral terminals of sensory nerves. (1)

Transport from the cell body can be slow and sensory axons can be very long. (So proteins can reach the terminal quicker).

Suggest a group of structures that can be referred to as 'spike initiators' in sensory neurones. (1)

Voltage-gated sodium channels

Fill the gaps relating to pain signalling in the nervous system. (8) ...................-threshold nociceptors are activated by intense ........................., ............................, or .......................... stimuli and feed this information to nociceptive neurones in the ..................................... Neurones then project via the ................... to cortical areas generating the sensory and emotional qualities of pain. These spinal cord pathways are subject to descending inhibitory and facilitatory influences from the ....................... Normally, activity in low-threshold afferents is carried by independent peripheral and central pathways and only generates ........................... sensations.

High mechanical thermal chemical spinal cord thalamus brainstem innocuous

Which laminae of the spinal cord receive inputs from nociceptors? (3)

I, II, V

Describe the type of input that is received by laminae I, II, and V of the spinal cord. (3)

I = pain only II = pain only V = integrates pain and innocuous input

Prostatic acid phosphatase (PAP) can be used as a marker to identify some sensory neurones. Describe the types of sensory neurones that can be identified using PAP staining. (1)

Nociceptive DRG neurones (peptidergic and non-peptidergic)

Briefly describe a method using rodents than can allow activity in the spinal cord to be measured. (4)

Rodent anaesthetised Electrode inserted into spinal cord Nociceptive stimuli applied to foot Spinal cord responses recorded

Briefly describe and explain the response expected when recording activity in the spinal cord when a painful stimulus is applied. (4)

Early response due to A fibres and a later response due to C fibres

Name the two general types of post-synaptic spinal neurone which are activated by painful stimuli. (2) Which is more common? (1)

Wide dynamic range (more common) Nociceptor specific

Give three alternative names for wide dynamic range neurones in the spinal cord. (3)

WDR type 2 convergent

In which lamina of the spinal cord are wide dynamic range neurones predominantly located? (1)

Lamina V

Describe the general role of wide dynamic range neurones in the spinal cord. (1) Describe how their firing relates to pain behaviour. (1)

They code stimulus intensity accurately from innocuous to painful range. In behavioural studies their firing correlates well with pain behaviour.

Give 2 alternative names for nociceptor specific neurones found in the spinal cord. (2)

NS type 3

What type/s of stimulus (noxious/innocuous) do nociceptor specific neurones in the spinal cord respond to? (1)

Noxious

Describe the proposed role of nociceptor specific neurones in the spinal cord. (1) Describe how their firing relates to pain behaviour. (1)

May be more important to transmit the general presence and localisation of pain rather than the intensity. Firing does not correlate with pain.

Name the major excitatory neurotransmitter used in the spinal cord (in the context of pain). (1)

Glutamate

Name the two receptors which allow fast glutamatergic synaptic transmission. (2)

AMPA Kainate

Which ion/s are AMPA and kainate receptors permeable to? (2)

Na Some subunits permeable to Ca

Which receptor is activated by A fibre and C fibre inputs to the spinal cord? (1) Describe how this receptor discriminates pain inputs from non-pain inputs. (1)

AMPA It does not

Describe how NMDA receptors are activated by pain. (1) What role do these receptors play in pain? (1)

Activated by sustained noxious input (removal of Mg block) Contribute to pain facilitation mechanisms

Which NMDA receptor subunits are the most common in the spinal cord? (2)

NMDAR1 NMDAR2B

Fill the gaps relating to NMDA receptors. (4) NMDA receptors feature a ........................... assembly of subunits. The common subunits are called ................ and ..................., and the subunits ................. can also feature in these receptors.

hetero-oligomeric GluN1 GluN2A-D GluN3A-B

As well as AMPA, NMDA, and kainate receptors, name another general type of receptor that can be activated by nociceptor inputs to the spinal cord. (1)

metabotropic glutamate receptors

Name the three groups of mGluR and state which subtypes feature in each group. (3)

Group I (mGluRs 1 and 5) Group II (mGluRs 2 and 3) Group III (mGluRs 4, 6, 7, 8)

Describe the G protein coupling and general downstream effects (including excitation/inhibition) of group I mGluRs. (3)

Coupled to Gq Activation of PLC and increased calcium Neuronal excitation

Describe how activation of group I mGluRs can affect other glutamate receptors. (1) Describe how they achieve this. (1)

Can enhance the effects of NMDA, AMPA, and kainate receptors They do this via phosphorylation

Describe the G protein coupling and general downstream effects (including excitation/inhibition) of group II mGluRs. (3)

Coupled to Gi Inhibition of adenylyl cyclase and decreased cAMP Inhibition

Describe the G protein coupling and general downstream effects (including excitation/inhibition) of group III mGluRs. (3)

Coupled to Gi Inhibition of adenylyl cyclase and decreased cAMP Inhibition

Which group/s of mGluRs can act as autoreceptors?

Group II and III

Given that group II and group III mGluRs are all inhibitory and decrease cAMP, explain why they are classed as separate groups. (1)

They have different pharmacological responses

Which mGluRs are present in the periphery on primary afferent fibres?

mGluR1 and 5 (Group I receptors)

Describe the phenomenon which would occur due to exogenous activation of group I mGluRs on primary afferent fibres. (1)

Hyperalgesia

Describe what the effect would be of applying mGluR1 and mGluR5 antagonists to peripheral primary afferent fibres. (1)

Inhibition of inflammatory pain responses

Which group of mGluRs are involved in central sensitisation in the spinal cord? (1)

Group I

Describe whether mGluR1 and mGluR5 are located pre- or postsynaptically in the spinal cord. (2)

mGluR1 = postsynaptic mGluR5 = pre and post synaptic

Which mGluRs have a role in normal nociceptive processing in the thalamus?

mGluR1 mGluR5

Describe the role that NMDA receptor blockade has in altering pain responses. (2)

Spinal NMDA antagonists attenuate facilitated pain responses (post-synaptic) No change in A or non-facilitated C fibre responses in spinal neurones (presynaptic)

Describe the concept of 'wind-up'. (2)

Spinal neurones show an increasing, exaggerated response to continued peripheral stimulus of the same intensity.

Describe how NMDA receptor blockade affects 'wind-up' in the spinal cord. (1)

Prevents wind-up

Name a pain process which can be contributed to by the process of 'wind-up'. (1)

Sensitisation

Which receptor does substance P bind to in the spinal cord? (1)

NK1

Define 'facilitation'. (1) Briefly explain the molecular process behind this phenomenon. (1)

Amplification of pain signals Neurotransmitters released from sensory neurones (eg. glutamate, SP) are able to increase the perception of pain

Define 'sensitisation'. (1) Briefly explain the molecular process behind this phenomenon. (1)

The CNS becomes more responsive to pain. The nervous system undergoes structural, functional, and chemical changes to make neurones more sensitive to noxious or innocuous stimuli.

True or false? Explain your answer if necessary. (1) Facilitation and sensitisation tend to influence each other, and the relationship can work in both directions.

True

Define 'pain'. (4)

An unpleasant sensory and emotional experience associated with, or resembling that associated with actual or potential tissue damage.

Very briefly describe the molecular mechanism behind acute pain. (1)

Activity in nociceptors

Describe the time scale of acute pain. (1)

Less than 3 months

Give two specific causes of chronic (ongoing acute) pain. (2)

Inflammation (eg. arthritis) Space occupying lesion (eg. tumour)

Very briefly describe the molecular mechanism behind chronic (ongoing acute) pain. (1)

Ongoing activity in nociceptors due to ongoing active pathology

Describe the time scale for chronic pain. (1)

Longer than 3-6 months

Chronic (ongoing acute) pain is often treatable with standard analgesics. Explain why it is still such a huge problem. (2)

Have to be careful with long-term treatment. Can produce behavioural changes (depression) and postural changes to guard the site of pain.

Briefly describe the pathology behind neurogenic/neuropathic pain. Give examples. (3)

Result of nerve damage eg. direct trauma such as wear and tear or illnesses such as diabetes or herpes (shingles)

True or false? Explain your answer if necessary. (1) Neurogenic/neuropathic pain is not necessarily the result of activity in nociceptors.

True

Neurogenic/neuropathic pain can sometimes resolve with appropriate treatment. Describe an issue with this treatment. (1)

We don't always understand why treatments work

Pain - The Basics Flashcards

(155 cards)