Sensory Pathways

Question 1

What is a sensory modality?

Answer 1

A type of stimulus (e.g hot, cold, touch).

Modalities have specialised receptors, transmit information through specific anatomical pathways to the brain.

Question 2

What are the types of receptors and their modalities?

Answer 2

Enclosed nerve endings:
Mechanoreceptors - touch, vibration, pressure and proprioception (joint position, muscle length, muscle tension)

Free nerve endings:

2) Thermoreceptor - temperature
3) Nociceptor - nociception (pain)

Question 3

What are the different classifications of sensory fibres?

Answer 3

Abeta - large fast conducting myelinated sensory fibres involved in transmitting innocuous mechanical stimulation.

Adelta - myelinated fast conducting sensory fibres but not as fast as Abetas because the have a smaller diameter. Involved in transducting pain and temperature. Nociceptors and thermoceptors

C - slow transducting, no myelination. Involved in the slower aching pain, (temperature and itch).

Together they build up a peripheral nerve

Question 4

Describe the sensory nerve endings

Answer 4

Individual axons within sensory fibres have modified terminals depending on the modalities.

C fibres unmyelinated with free endings - for heat

Abeta myelinated with nerve endings encapsulated in
layers of connective tissue - mechanoreceptors

Question 5

Define sensory receptors?

Answer 5

They are transducers - convert energy from the environment into neuronal action potentials

Question 6

Define absolute threshold?

Answer 6

The level of stimulus that produces a positive response of detection 50% of the time. If the stimulus is strong enough it will generate a generator potential that will illicit a train of action potentials

Question 7

What happens if you give a stronger stimulus? What happens if you increase the stimulus strength and duration?

Answer 7

A larger generator potential is produced which cause a train of AP with increased frequency and duration –> more neurotransmitter is released

Increased stimulus strength and duration = increased neurotransmitter release = greater intensity

Question 8

Describe the thermoreceptors?

Answer 8

TRP ion channels - transient receptor potential (TRP) ion channels.

Free nerve endings with high thermal sensitivity.

There are 4 heat-activated channels (TRPV1-4) and 2 cold activated TRP channels (TRPM8, TRPA1)

Question 9

What are the different kinds of mechanoreceptors?

Answer 9

Meissner’s corpuscle - fine discriminative touch, low frequency vibration
Merkell cells - light touch and superficial pressure
Pacinian corpuscle - detects deep pressure, high frequency vibration and tickling
Rufini endings - continuous pressure or touch and stretch

Question 10

What are tonic receptors?

Answer 10

They detect continuous stimulus strength - don’t adapt or adapt very slowly.

They continue to transmit impulses to the brain as long as the stimulus is present which keeps the brain constantly informed of the status of the body.

Merkel cells - slowly adapt allowing for fine touch to be perceived. Stroking

Question 11

What are phasic receptors?

Answer 11

Detect a change in stimulus strength - adapt quickly They transmit impulses at the start and at the end of the stimulus.

Pacinian receptor - sudden pressure excites receptor which transmits a signal again when pressure is released.

Question 12

What are the receptive fields?

Answer 12

Region on the skin which causes activation of a single sensory neuron when activated. There are different sizes of receptive fields.

Small receptive fields allow for the detection of fine detail over a small area. Precise perception (arms). The fingers have many densely packed mechanoreceptors (with small receptive fields)
The back has large receptive fields that allow the cell to detect changes over a wider area (less precise perception)

See slides for diagrams of receptive fields

Question 13

What is two point discrimination?

Answer 13

Minimum distance at which two points are perceived as separate - related to the size of the perceptive field.

See slide for diagram

Question 14

Describe the dorsal root

Answer 14

See diagrams on slide

Cell bodies are in the dorsal root ganglia (body) and trigeminal ganglia (face). After the DRG the sensory fibres enter the dorsal horn.

Question 15

Describe the dorsal horn

Answer 15

It is organised into Rexed Laminae (I-VII). See slides
Innocuous mechanical stimuli - Abeta fibres terminate in lamina III-VI (deep)
Pain and temperature stimuli - Adelta and C fibres terminate in lamina I-II (superficial)

There are two main types of dorsal horn neurones:

1) Those with axons that project to the brain (projection neurones)
2) Those with axons that remain in the spinal cord (interneurones - connect different laminae)

Question 16

What is lateral inhibition?

Answer 16

Receptive fields can overlap making it difficult to distinguish between 2 stimulus locations. Lateral inhibition prevents the overlap of the receptive fields and facilitates pinpoint accuracy in localisation of the stimulus.

Mediated by inhibitory interneurones within the dorsal horn of the spinal cord.

The difference between adjacent inputs is enhanced by lateral inhibition

Facilitates enhanced sensory perception (discrimination)

Question 17

Describe the gate control theory

Answer 17

Inhibition of primary afferent inputs (C fibres/Adelta fibres PAIN) before they are transmitted to the brain.

See diagram - Abeta fibre can stimulate a inhibitory interneurone that can inhibit the projection neurone going to the brain.

Question 18

Label the central sensory structures of the brain

Answer 18

See diagram
SI - primary somatosensory cortex (in postcentral gryus)
SII - secondary somatosensory cortex (in parietal operculum)
Posterior parietal cortex = spatial awareness of body

Question 19

What is the dorsal column system?

Answer 19

Transmits the innocuous mechanical stimuli (vibration, fine discriminative touch)

Abeta fibres enter via the dorsal horn and enter the ascending dorsal column pathway.

Information conveyed from the lower limbs and body (below T6) travel ipsilaterally along the gracile tract. Above T6: ipsilaterally along the cuneate tract. See diagram

Question 20

Describe the 1st order neurones - DC

Answer 20

They teminate in the medulla:
Fibres in the gracile tract first synapse in the gracile nucleus.
Fibres in the cunate tract first synapse in the cunate nucleus.
See diagrams

Question 21

Describe the 2nd order neurones - DC

Answer 21

They decussate (cross the midline) in the caudal medulla and form the contralateral medial lemniscus tract. Topographic representation

The axons of the 2nd order neurones terminate in the ventral posterior lateral nucleus of the thalamus. (lower extremities terminate more lateral - topographic representation of the body in the VPL)

See diagrams

Question 22

Describe the 3rd order neurones - DC

Answer 22

3rd order neurones from the VPL project to the somatosensory cortex

The size of somatotopic areas is proportional to density of sensory receptors in that body region (somatosensory homunculus)

Question 23

What is the spinothalamic (anterolateral) pathway? Pain, temperature and crude touch

Answer 23

There are two pathways in the spinothalamic pathway:
Pain and temperature sensations ascend within the lateral spinothalamic tract.
Crude touch ascends within the anterior spinothalamic tract.

Question 24

Describe the 1st order neurones - ST

Answer 24

1st order neurones terminate on entering the dorsal horn. The 2nd order neurones decussate immediately in the spinal cord and form the spinothalamic tract.
See diagram

Question 25

Describe the 2nd order neurones - ST

Answer 25

They terminate in ventral posterior lateral nucleus of the thalamus.

Question 26

What are the key differences between the dorsal column and spinothalamic tract

Answer 26

Spinothalamic tract - pain, temperature, crude touch.
- Crosses in the spinal cord

Dorsal column pathway - light touch, vibration, 2 point discrimination.
- Crosses in the brain stem

Should be aware that pain is also linked to emotion not just sensory. Spinoreticular tract - terminates parabrachial area then limbic system

Question 27

What is the pain matrix?

Answer 27

Functional MRI (fMRI) has shown there is a ‘cerebral signature for pain’

1) Cortex:
- SI
- SII
- Insula cortex
- Anterior cingulate cortex
- Prefrontal cortex
2) Amygdala
3) Cerebellum
4) Brainstem

Question 28

How is quantitative sensory testing used to test the integrity of the ascending pathways?

Answer 28

You what kind of stimulation affects which tract - damage to tract means the stimulation will not be felt.

spinothalamic tract - temperature and pain

dorsal column system - discriminative touch –> 2 point discrimination

Using QST combined with questionnaires is an effect way of diagnosing people with neuropathic pain

Question 29

How would you know if there was an anterior spinal cord lesion?

Answer 29

Blocked anterior spinal artery causes ischaemic damage to the anterior part of the spinal cord.
Spinothalamic tract becomes damaged –> bilateral loss of pain and temperature below the level of the lesion.

However the dorsal column system remains intact therefore retained light touch, vibration and 2 point discrimination

Question 30

Describe nociceptors

Answer 30

Aδ fibers mediate sharp, intense or first pain

• Type 1: noxious mechanical (pain)
• Type 2: noxious heat

C-fibres mediate dull, aching or second pain
- Noxious thermal, mechanical and chemical stimuli (polymodal)

Question 31

Define pain

Answer 31

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

Question 32

Define allodynia

Answer 32

Pain due to a stimulus that does not normally provoke pain

Question 33

Define hyperalgesia

Answer 33

Increased pain from a stimulus that normally provokes pain

See graph

Primary and secondary hyperalgesia

Question 34

Peripheral sensitisation vs central sensitisation

Answer 34

Peripheral sensitisation:
There are inflammatory changes which occur at the nerve endings of C-fibres. Inflammatory mediators such as bradykinin, histamine etc. all bind to receptors and cause the properties of C-fibres to change (i.e. they have a lower activation threshold for painful stimuli which manifests as primary hyperalgesia).

Central sensitisation: this refers to the changes which occur in the spinal cord during chronic pain. On-going activation of c-fibers causes a form of NMDA receptor mediated synaptic plasticity (similar to LTP in memory). This causes changes in the central processing of adjacent A-delta fibres, which results in the spread of sensitivity away from the injury site on the skin (i.e. secondary hyperalgesia).

Question 35

Describe spinal cord nociceptive processing

Answer 35

Adelta and C fibres synapse superficially in the dorsal horn. Rexed lamina I and II.

Nociception is initiated by NMDA receptor activation
Persistent activation of NMDA receptor can result in the development of chronic pain (e.g arthritis)

LOSS of inhibitory influences

Question 36

Describe descending pain modulation?

Answer 36

Monoamines are released from the brain stem to inhibit spinal cord excitability. (inhibits pain)

1) PAG-RVM (rostral ventromedial medulla) axis - main NT involved serotonin (harmful pain)
2) LC (locus cereleus in the pons) - noradrenaline (protective - inhibits signalling from the dorsal horn)

Placebo can activate descending inhibition in humans
There is a balance between an adrenergic and serotonin effect. See Pharm opiods

Question 37

How do endogenous opioids affect descending pain modulation?

Answer 37

The PAG and RVM contain high concentrations of u-opoid receptors. Endogenous opiods enhance the inhibition from the PAG-RVM axis.

Reduces pain transmission in the dorsal horn by inhibiting glutamate release

Forms part of the endogenous analgesic system

Question 38

What drugs can target the descending control systems for pain relief?

Answer 38

Opioids - PAG and RVM. u-opioid receptors
Antidepressants - TCA, SSRI and SNRI (they would work because the inhibit the reuptake of monoamines.)

SSRI are not that effective while TCAs are much more effective. This shows that NA is much more important in the descending control of pain.

Question 39

How does chronic pain affect the descending control system?

Answer 39

During chronic pain there are changes in descending control systems. Descending noradrenergic pathways are protective and loss of this control is associated with the development of chronic pain. Similarly, there is a shift towards descending facilitation in chronic pain patients.

Descending inhibition is lost in chronic pain patients.

Duloxetine enhances the action of noradrenaline in the spinal cord and conditioned pain modulation provides a means by which to predict who will respond best to the drug (i.e. those which had deficient descending inhibition).